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  • 1. Amundadottir, Laufey
    et al.
    Kraft, Peter
    Stolzenberg-Solomon, Rachael Z
    Fuchs, Charles S
    Petersen, Gloria M
    Arslan, Alan A
    Bueno-de-Mesquita, H Bas
    Gross, Myron
    Helzlsouer, Kathy
    Jacobs, Eric J
    Lacroix, Andrea
    Zheng, Wei
    Albanes, Demetrius
    Bamlet, William
    Berg, Christine D
    Berrino, Franco
    Bingham, Sheila
    Buring, Julie E
    Bracci, Paige M
    Canzian, Federico
    Clavel-Chapelon, Françoise
    Clipp, Sandra
    Cotterchio, Michelle
    de Andrade, Mariza
    Duell, Eric J
    Fox Jr, John W
    Gallinger, Steven
    Gaziano, J Michael
    Giovannucci, Edward L
    Goggins, Michael
    González, Carlos A
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hankinson, Susan E
    Hassan, Manal
    Holly, Elizabeth A
    Hunter, David J
    Hutchinson, Amy
    Jackson, Rebecca
    Jacobs, Kevin B
    Jenab, Mazda
    Kaaks, Rudolf
    Klein, Alison P
    Kooperberg, Charles
    Kurtz, Robert C
    Li, Donghui
    Lynch, Shannon M
    Mandelson, Margaret
    McWilliams, Robert R
    Mendelsohn, Julie B
    Michaud, Dominique S
    Olson, Sara H
    Overvad, Kim
    Patel, Alpa V
    Peeters, Petra H M
    Rajkovic, Aleksandar
    Riboli, Elio
    Risch, Harvey A
    Shu, Xiao-Ou
    Thomas, Gilles
    Tobias, Geoffrey S
    Trichopoulos, Dimitrios
    Van Den Eeden, Stephen K
    Virtamo, Jarmo
    Wactawski-Wende, Jean
    Wolpin, Brian M
    Yu, Herbert
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Chanock, Stephen J
    Hartge, Patricia
    Hoover, Robert N
    Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.2009Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, ISSN EISSN: 1546-1718, Vol. 41, s. 986-990Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

  • 2. Bentley, Amy R.
    et al.
    Sung, Yun J.
    Brown, Michael R.
    Winkler, Thomas W.
    Kraja, Aldi T.
    Ntalla, Ioanna
    Schwander, Karen
    Chasman, Daniel, I
    Lim, Elise
    Deng, Xuan
    Guo, Xiuqing
    Liu, Jingmin
    Lu, Yingchang
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Huffman, Jennifer E.
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Richard, Melissa A.
    Noordam, Raymond
    Baker, Jenna
    Chen, Guanjie
    Aschard, Hugues
    Bartz, Traci M.
    Ding, Jingzhong
    Dorajoo, Rajkumar
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert, V
    Tajuddin, Salman M.
    Zhao, Wei
    Graff, Mariaelisa
    Alver, Maris
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Evangelou, Evangelos
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    Hartwig, Fernando P.
    He, Meian
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Hung, Yi-Jen
    Jackson, Anne U.
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuehnel, Brigitte
    Leander, Karin
    Lin, Keng-Hung
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Matoba, Nana
    Nolte, Ilja M.
    Pietzner, Maik
    Prins, Bram
    Riaz, Muhammad
    Robino, Antonietta
    Said, M. Abdullah
    Schupf, Nicole
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Tzung-Dau
    Wang, Yajuan
    Ware, Erin B.
    Wen, Wanqing
    Xiang, Yong-Bing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Adeyemo, Adebowale
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Arzumanyan, Zorayr
    Aung, Tin
    Ballantyne, Christie
    Barr, R. Graham
    Bielak, Lawrence F.
    Boerwinkle, Eric
    Bottinger, Erwin P.
    Broeckel, Ulrich
    Brown, Morris
    Cade, Brian E.
    Campbell, Archie
    Canouil, Mickael
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Christensen, Kaare
    Concas, Maria Pina
    Connell, John M.
    de las Fuentes, Lisa
    de Silva, H. Janaka
    de Vries, Paul S.
    Doumatey, Ayo
    Duan, Qing
    Eaton, Charles B.
    Eppinga, Ruben N.
    Faul, Jessica D.
    Floyd, James S.
    Forouhi, Nita G.
    Forrester, Terrence
    Friedlander, Yechiel
    Gandin, Ilaria
    Gao, He
    Ghanbari, Mohsen
    Gharib, Sina A.
    Gigante, Bruna
    Giulianini, Franco
    Grabe, Hans J.
    Gu, C. Charles
    Harris, Tamara B.
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hixson, James E.
    Ikram, M. Arfan
    Jia, Yucheng
    Joehanes, Roby
    Johnson, Craig
    Jonas, Jost Bruno
    Justice, Anne E.
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Kolcic, Ivana
    Kooperberg, Charles
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Liang, Jingjing
    Lin, Shiow
    Liu, Ching-Ti
    Liu, Jianjun
    Liu, Kiang
    Loh, Marie
    Lohman, Kurt K.
    Louie, Tin
    Luzzi, Anna
    Magi, Reedik
    Mahajan, Anubha
    Manichaikul, Ani W.
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Momozawa, Yukihide
    Morris, Andrew P.
    Murray, Alison D.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    North, Kari E.
    O'Connell, Jeffrey R.
    Palmer, Nicholette D.
    Papanicolau, George J.
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Poulter, Neil
    Raitakari, Olli T.
    Reiner, Alex P.
    Renstrom, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
    Rice, Treva K.
    Rich, Stephen S.
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rosendaal, Frits R.
    Rudan, Igor
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Sever, Peter
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Stringham, Heather M.
    Tan, Nicholas Y. Q.
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Tiemeier, Henning
    Turner, Stephen T.
    Uitterlinden, Andre G.
    van Heemst, Diana
    Waldenberger, Melanie
    Wang, Heming
    Wang, Lan
    Wang, Lihua
    Wei, Wen Bin
    Williams, Christine A.
    Wilson, Gregory, Sr.
    Wojczynski, Mary K.
    Yao, Jie
    Young, Kristin
    Yu, Caizheng
    Yuan, Jian-Min
    Zhou, Jie
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Cooper, Richard S.
    de Faire, Ulf
    Deary, Ian J.
    Elliott, Paul
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Return to work after interdisciplinary pain rehabilitation Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA; OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
    Freedman, Barry, I
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo L.
    Juang, Jyh-Ming Jimmy
    Kamatani, Yoichiro
    Kammerer, Candace M.
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Laurie, Cathy C.
    Lee, I-Te
    Lehtimaki, Terho
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Pereira, Alexandre C.
    Rauramaa, Rainer
    Redline, Susan
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wang, Jun-Sing
    Wang, Ya Xing
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zeggini, Eleftheria
    Zheng, Wei
    Bouchard, Claude
    Evans, Michele K.
    Gudnason, Vilmundur
    Kardia, Sharon L. R.
    Liu, Yongmei
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Province, Michael A.
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Loos, Ruth J. F.
    Franceschini, Nora
    Rotter, Jerome, I
    Zhu, Xiaofeng
    Bierut, Laura J.
    Gauderman, W. James
    Rice, Kenneth
    Munroe, Patricia B.
    Morrison, Alanna C.
    Rao, Dabeeru C.
    Rotimi, Charles N.
    Cupples, L. Adrienne
    Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids2019Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 4, s. 636-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

  • 3. Berndt, Sonja I.
    et al.
    Gustafsson, Stefan
    Maegi, Reedik
    Ganna, Andrea
    Wheeler, Eleanor
    Feitosa, Mary F.
    Justice, Anne E.
    Monda, Keri L.
    Croteau-Chonka, Damien C.
    Day, Felix R.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gentilini, Davide
    Jackson, Anne U.
    Luan, Jian'an
    Randall, Joshua C.
    Vedantam, Sailaja
    Willer, Cristen J.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Hu, Yi-Juan
    Lee, Sang Hong
    Liang, Liming
    Lin, Dan-Yu
    Min, Josine L.
    Neale, Benjamin M.
    Thorleifsson, Gudmar
    Yang, Jian
    Albrecht, Eva
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Cadby, Gemma
    den Heijer, Martin
    Eklund, Niina
    Fischer, Krista
    Goel, Anuj
    Hottenga, Jouke-Jan
    Huffman, Jennifer E.
    Jarick, Ivonne
    Johansson, Asa
    Johnson, Toby
    Kanoni, Stavroula
    Kleber, Marcus E.
    Koenig, Inke R.
    Kristiansson, Kati
    Kutalik, Zoltn
    Lamina, Claudia
    Lecoeur, Cecile
    Li, Guo
    Mangino, Massimo
    McArdle, Wendy L.
    Medina-Gomez, Carolina
    Mueller-Nurasyid, Martina
    Ngwa, Julius S.
    Nolte, Ilja M.
    Paternoster, Lavinia
    Pechlivanis, Sonali
    Perola, Markus
    Peters, Marjolein J.
    Preuss, Michael
    Rose, Lynda M.
    Shi, Jianxin
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smith, Albert Vernon
    Strawbridge, Rona J.
    Surakka, Ida
    Teumer, Alexander
    Trip, Mieke D.
    Tyrer, Jonathan
    Van Vliet-Ostaptchouk, Jana V.
    Vandenput, Liesbeth
    Waite, Lindsay L.
    Zhao, Jing Hua
    Absher, Devin
    Asselbergs, Folkert W.
    Atalay, Mustafa
    Attwood, Antony P.
    Balmforth, Anthony J.
    Basart, Hanneke
    Beilby, John
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Bruinenberg, Marcel
    Campbell, Harry
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Connell, John M.
    Cookson, William O.
    de Faire, Ulf
    de Vegt, Femmie
    Dei, Mariano
    Dimitriou, Maria
    Edkins, Sarah
    Estrada, Karol
    Evans, David M.
    Farrall, Martin
    Ferrario, Marco M.
    Ferrieres, Jean
    Franke, Lude
    Frau, Francesca
    Gejman, Pablo V.
    Grallert, Harald
    Groenberg, Henrik
    Gudnason, Vilmundur
    Hall, Alistair S.
    Hall, Per
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Hebebrand, Johannes
    Homuth, Georg
    Hu, Frank B.
    Hunt, Sarah E.
    Hyppoenen, Elina
    Iribarren, Carlos
    Jacobs, Kevin B.
    Jansson, John-Olov
    Jula, Antti
    Kahonen, Mika
    Kathiresan, Sekar
    Kee, Frank
    Khaw, Kay-Tee
    Kivimaki, Mika
    Koenig, Wolfgang
    Kraja, Aldi T.
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laitinen, Jaana H.
    Lakka, Timo A.
    Langenberg, Claudia
    Launer, Lenore J.
    Lind, Lars
    Lindstrom, Jaana
    Liu, Jianjun
    Liuzzi, Antonio
    Lokki, Marja-Liisa
    Lorentzon, Mattias
    Madden, Pamela A.
    Magnusson, Patrik K.
    Manunta, Paolo
    Marek, Diana
    Maerz, Winfried
    Leach, Irene Mateo
    McKnight, Barbara
    Medland, Sarah E.
    Mihailov, Evelin
    Milani, Lili
    Montgomery, Grant W.
    Mooser, Vincent
    Muehleisen, Thomas W.
    Munroe, Patricia B.
    Musk, Arthur W.
    Narisu, Narisu
    Navis, Gerjan
    Nicholson, George
    Nohr, Ellen A.
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Colin N. A.
    Palotie, Aarno
    Peden, John F.
    Pedersen, Nancy
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Prokopenko, Inga
    Puetter, Carolin
    Radhakrishnan, Aparna
    Raitakari, Olli
    Rendon, Augusto
    Rivadeneira, Fernando
    Rudan, Igor
    Saaristo, Timo E.
    Sambrook, Jennifer G.
    Sanders, Alan R.
    Sanna, Serena
    Saramies, Jouko
    Schipf, Sabine
    Schreiber, Stefan
    Schunkert, Heribert
    Shin, So-Youn
    Signorini, Stefano
    Sinisalo, Juha
    Skrobek, Boris
    Soranzo, Nicole
    Stancakova, Alena
    Stark, Klaus
    Stephens, Jonathan C.
    Stirrups, Kathleen
    Stolk, Ronald P.
    Stumvoll, Michael
    Swift, Amy J.
    Theodoraki, Eirini V.
    Thorand, Barbara
    Tregouet, David-Alexandre
    Tremoli, Elena
    Van der Klauw, Melanie M.
    van Meurs, Joyce B. J.
    Vermeulen, Sita H.
    Viikari, Jorma
    Virtamo, Jarmo
    Vitart, Veronique
    Waeber, Gerard
    Wang, Zhaoming
    Widen, Elisabeth
    Wild, Sarah H.
    Willemsen, Gonneke
    Winkelmann, Bernhard R.
    Witteman, Jacqueline C. M.
    Wolffenbuttel, Bruce H. R.
    Wong, Andrew
    Wright, Alan F.
    Zillikens, M. Carola
    Amouyel, Philippe
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Boomsma, Dorret I.
    Caulfield, Mark J.
    Chanock, Stephen J.
    Cupples, L. Adrienne
    Cusi, Daniele
    Dedoussis, George V.
    Erdmann, Jeanette
    Eriksson, Johan G.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Froguel, Philippe
    Gieger, Christian
    Gyllensten, Ulf
    Hamsten, Anders
    Harris, Tamara B.
    Hengstenberg, Christian
    Hicks, Andrew A.
    Hingorani, Aroon
    Hinney, Anke
    Hofman, Albert
    Hovingh, Kees G.
    Hveem, Kristian
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Levinson, Douglas F.
    Martin, Nicholas G.
    Metspalu, Andres
    Morris, Andrew D.
    Nieminen, Markku S.
    Njolstad, Inger
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ouwehand, Willem H.
    Palmer, Lyle J.
    Penninx, Brenda
    Power, Chris
    Province, Michael A.
    Psaty, Bruce M.
    Qi, Lu
    Rauramaa, Rainer
    Ridker, Paul M.
    Ripatti, Samuli
    Salomaa, Veikko
    Samani, Nilesh J.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Timothy D.
    Stefansson, Kari
    Tonjes, Anke
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Vollenweider, Peter
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F.
    Abecasis, Goncalo R.
    Assimes, Themistocles L.
    Barroso, Ines
    Boehnke, Michael
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Frayling, Timothy
    Groop, Leif C.
    Haritunian, Talin
    Heid, Iris M.
    Hunter, David
    Kaplan, Robert C.
    Karpe, Fredrik
    Moffatt, Miriam F.
    Mohlke, Karen L.
    O'Connell, Jeffrey R.
    Pawitan, Yudi
    Schadt, Eric E.
    Schlessinger, David
    Steinthorsdottir, Valgerdur
    Strachan, David P.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Visscher, Peter M.
    Di Blasio, Anna Maria
    Hirschhorn, Joel N.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Meyre, David
    Scherag, Andr
    McCarthy, Mark I.
    Speliotes, Elizabeth K.
    North, Kari E.
    Loos, Ruth J. F.
    Ingelsson, Erik
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture2013Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 5, s. 501-U69Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

  • 4. Bojesen, Stig E.
    et al.
    Pooley, Karen A.
    Johnatty, Sharon E.
    Beesley, Jonathan
    Michailidou, Kyriaki
    Tyrer, Jonathan P.
    Edwards, Stacey L.
    Pickett, Hilda A.
    Shen, Howard C.
    Smart, Chanel E.
    Hillman, Kristine M.
    Mai, Phuong L.
    Lawrenson, Kate
    Stutz, Michael D.
    Lu, Yi
    Karevan, Rod
    Woods, Nicholas
    Johnstonw, Rebecca L.
    French, Juliet D.
    Chen, Xiaoqing
    Weischer, Maren
    Nielsen, Sune F.
    Maranian, Melanie J.
    Ghoussaini, Maya
    Ahmed, Shahana
    Baynes, Caroline
    Bolla, Manjeet K.
    Wang, Qin
    Dennis, Joe
    McGuffog, Lesley
    Barrowdale, Daniel
    Lee, Andrew
    Healey, Sue
    Lush, Michael
    Tessier, Daniel C.
    Vincent, Daniel
    Bacot, Francis
    Vergote, Ignace
    Lambrechts, Sandrina
    Despierre, Evelyn
    Risch, Harvey A.
    Gonzalez-Neira, Anna
    Rossing, Mary Anne
    Pita, Guillermo
    Doherty, Jennifer A.
    Alvarez, Nuria
    Larson, Melissa C.
    Fridley, Brooke L.
    Schoof, Nils
    Chang-Claude, Jenny
    Cicek, Mine S.
    Peto, Julian
    Kalli, Kimberly R.
    Broeks, Annegien
    Armasu, Sebastian M.
    Schmidt, Marjanka K.
    Braaf, Linde M.
    Winterhoff, Boris
    Nevanlinna, Heli
    Konecny, Gottfried E.
    Lambrechts, Diether
    Rogmann, Lisa
    Guenel, Pascal
    Teoman, Attila
    Milne, Roger L.
    Garcia, Joaquin J.
    Cox, Angela
    Shridhar, Vijayalakshmi
    Burwinkel, Barbara
    Marme, Frederik
    Hein, Rebecca
    Sawyer, Elinor J.
    Haiman, Christopher A.
    Wang-Gohrke, Shan
    Andrulis, Irene L.
    Moysich, Kirsten B.
    Hopper, John L.
    Odunsi, Kunle
    Lindblom, Annika
    Giles, Graham G.
    Brenner, Hermann
    Simard, Jacques
    Lurie, Galina
    Fasching, Peter A.
    Carney, Michael E.
    Radice, Paolo
    Wilkens, Lynne R.
    Swerdlow, Anthony
    Goodman, Marc T.
    Brauch, Hiltrud
    Garcia-Closas, Montserrat
    Hillemanns, Peter
    Winqvist, Robert
    Durst, Matthias
    Devilee, Peter
    Runnebaum, Ingo
    Jakubowska, Anna
    Lubinski, Jan
    Mannermaa, Arto
    Butzow, Ralf
    Bogdanova, Natalia V.
    Doerk, Thilo
    Pelttari, Liisa M.
    Zheng, Wei
    Leminen, Arto
    Anton-Culver, Hoda
    Bunker, Clareann H.
    Kristensen, Vessela
    Ness, Roberta B.
    Muir, Kenneth
    Edwards, Robert
    Meindl, Alfons
    Heitz, Florian
    Matsuo, Keitaro
    du Bois, Andreas
    Wu, Anna H.
    Harter, Philipp
    Teo, Soo-Hwang
    Schwaab, Ira
    Shu, Xiao-Ou
    Blot, William
    Hosono, Satoyo
    Kang, Daehee
    Nakanishi, Toru
    Hartman, Mikael
    Yatabe, Yasushi
    Hamann, Ute
    Karlan, Beth Y.
    Sangrajrang, Suleeporn
    Kjaer, Susanne Kruger
    Gaborieau, Valerie
    Jensen, Allan
    Eccles, Diana
    Hogdall, Estrid
    Shen, Chen-Yang
    Brown, Judith
    Woo, Yin Ling
    Shah, Mitul
    Azmi, Mat Adenan Noor
    Luben, Robert
    Omar, Siti Zawiah
    Czene, Kamila
    Vierkant, Robert A.
    Nordestgaard, Borge G.
    Flyger, Henrik
    Vachon, Celine
    Olson, Janet E.
    Wang, Xianshu
    Levine, Douglas A.
    Rudolph, Anja
    Weber, Rachel Palmieri
    Flesch-Janys, Dieter
    Iversen, Edwin
    Nickels, Stefan
    Schildkraut, Joellen M.
    Silva, Isabel Dos Santos
    Cramer, Daniel W.
    Gibson, Lorna
    Terry, Kathryn L.
    Fletcher, Olivia
    Vitonis, Allison F.
    van der Schoot, C. Ellen
    Poole, Elizabeth M.
    Hogervorst, Frans B. L.
    Tworoger, Shelley S.
    Liu, Jianjun
    Bandera, Elisa V.
    Li, Jingmei
    Olson, Sara H.
    Humphreys, Keith
    Row, Irene
    Blomqvist, Carl
    Rodriguez-Rodriguez, Lorna
    Aittomaki, Kristiina
    Salvesen, Helga B.
    Muranen, Taru A.
    Wik, Elisabeth
    Brouwers, Barbara
    Krakstad, Camilla
    Wauters, Els
    Halle, Mari K.
    Wildiers, Hans
    Kiemeney, Lambertus A.
    Mulot, Claire
    Aben, Katja K.
    Laurent-Puig, Pierre
    Altena, Anne Mvan
    Truong, Therese
    Massuger, Leon F. A. G.
    Benitez, Javier
    Pejovic, Tanja
    Arias Perez, Jose Ignacio
    Hoatlin, Maureen
    Zamora, M. Pilar
    Cook, Linda S.
    Balasubramanian, Sabapathy P.
    Kelemen, Linda E.
    Schneeweiss, Andreas
    Le, Nhu D.
    Sohn, Christof
    Brooks-Wilson, Angela
    Tomlinson, Ian
    Kerin, Michael J.
    Miller, Nicola
    Cybulski, Cezary
    Henderson, Brian E.
    Menkiszak, Janusz
    Schumacher, Fredrick
    Wentzensen, Nicolas
    Marchand, Loic Le
    Yang, Hannah P.
    Mulligan, Anna Marie
    Glendon, Gord
    Engelholm, Svend Aage
    Knight, Julia A.
    Hogdall, Claus K.
    Apicella, Carmel
    Gore, Martin
    Tsimiklis, Helen
    Song, Honglin
    Southey, Melissa C.
    Jager, Agnes
    den Ouweland, Ans M. Wvan
    Brown, Robert
    Martens, John W. M.
    Flanagan, James M.
    Kriege, Mieke
    Paul, James
    Margolin, Sara
    Siddiqui, Nadeem
    Severi, Gianluca
    Whittemore, Alice S.
    Baglietto, Laura
    McGuire, Valerie
    Stegmaier, Christa
    Sieh, Weiva
    Mueller, Heiko
    Arndt, Volker
    Labreche, France
    Gao, Yu-Tang
    Goldberg, Mark S.
    Yang, Gong
    Dumont, Martine
    McLaughlin, John R.
    Hartmann, Arndt
    Ekici, Arif B.
    Beckmann, Matthias W.
    Phelan, Catherine M.
    Lux, Michael P.
    Permuth-Wey, Jenny
    Peissel, Bernard
    Sellers, Thomas A.
    Ficarazzi, Filomena
    Barile, Monica
    Ziogas, Argyrios
    Ashworth, Alan
    Gentry-Maharaj, Aleksandra
    Jones, Michael
    Ramus, Susan J.
    Orr, Nick
    Menon, Usha
    Pearce, Celeste L.
    Bruening, Thomas
    Pike, Malcolm C.
    Ko, Yon-Dschun
    Lissowska, Jolanta
    Figueroa, Jonine
    Kupryjanczyk, Jolanta
    Chanock, Stephen J.
    Dansonka-Mieszkowska, Agnieszka
    Jukkola-Vuorinen, Arja
    Rzepecka, Iwona K.
    Pylkas, Katri
    Bidzinski, Mariusz
    Kauppila, Saila
    Hollestelle, Antoinette
    Seynaeve, Caroline
    Tollenaar, Rob A. E. M.
    Durda, Katarzyna
    Jaworska, Katarzyna
    Hartikainen, Jaana M.
    Kosma, Veli-Matti
    Kataja, Vesa
    Antonenkova, Natalia N.
    Long, Jirong
    Shrubsole, Martha
    Deming-Halverson, Sandra
    Lophatananon, Artitaya
    Siriwanarangsan, Pornthep
    Stewart-Brown, Sarah
    Ditsch, Nina
    Lichtner, Peter
    Schmutzler, Rita K.
    Ito, Hidemi
    Iwata, Hiroji
    Tajima, Kazuo
    Tseng, Chiu-Chen
    Stram, Daniel O.
    van den Berg, David
    Yip, Cheng Har
    Ikrarn, M. Kamran
    Teh, Yew-Ching
    Cai, Hui
    Lu, Wei
    Signorello, Lisa B.
    Cai, Qiuyin
    Noh, Dong-Young
    Yoo, Keun-Young
    Miao, Hui
    Iau, Philip Tsau-Choong
    Teo, Yik Ying
    McKay, James
    Shapiro, Charles
    Ademuyiwa, Foluso
    Fountzilas, George
    Hsiung, Chia-Ni
    Yu, Jyh-Cherng
    Hou, Ming-Feng
    Healey, Catherine S.
    Luccarini, Craig
    Peock, Susan
    Stoppa-Lyonnet, Dominique
    Peterlongo, Paolo
    Rebbeck, Timothy R.
    Piedmonte, Marion
    Singer, Christian F.
    Friedman, Eitan
    Thomassen, Mads
    Offit, Kenneth
    Hansen, Thomas V. O.
    Neuhausen, Susan L.
    Szabo, Csilla I.
    Blanco, Ignacio
    Garber, Judy
    Narod, Steven A.
    Weitzel, Jeffrey N.
    Montagna, Marco
    Olah, Edith
    Godwin, Andrew K.
    Yannoukakos, Drakoulis
    Goldgar, David E.
    Caldes, Trinidad
    Imyanitov, Evgeny N.
    Tihomirova, Laima
    Arun, Banu K.
    Campbell, Ian
    Mensenkamp, Arjen R.
    van Asperen, Christi J.
    van Roozendaa, Kees E. P.
    Meijers-Heijboer, Hanne
    Collee, J. Margriet
    Oosterwijk, Jan C.
    Hooning, Maartje J.
    Rookus, Matti A.
    van der Luijt, Rob B.
    Os, Theo A. Mvan
    Evans, D. Gareth
    Frost, Debra
    Fineberg, Elena
    Barwell, Julian
    Walker, Lisa
    Kennedy, M. John
    Platte, Radka
    Davidson, Rosemarie
    Ellis, Steve D.
    Cole, Trevor
    Bressac-de Paillerets, Brigitte
    Buecher, Bruno
    Damiola, Francesca
    Faivre, Laurence
    Frenay, Marc
    Sinilnikova, Olga M.
    Caron, Olivier
    Giraud, Sophie
    Mazoyer, Sylvie
    Bonadona, Valerie
    Caux-Moncoutier, Virginie
    Toloczko-Grabarek, Aleksandra
    Gronwald, Jacek
    Byrski, Tomasz
    Spurdle, Amanda B.
    Bonanni, Bernardo
    Zaffaroni, Daniela
    Giannini, Giuseppe
    Bernard, Loris
    Dolcetti, Riccardo
    Manoukian, Siranoush
    Arnold, Norbert
    Engel, Christoph
    Deissler, Helmut
    Rhiem, Kerstin
    Niederacher, Dieter
    Pendl, Hansjoerg
    Sutter, Christian
    Wappenschmidt, Barbara
    Borg, Ake
    Mein, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rantala, Johanna
    Soller, Maria
    Nathanson, Katherine L.
    Domchek, Susan M.
    Rodriguez, Gustavo C.
    Salani, Ritu
    Kaulich, Daphne Gschwantler
    Tea, Muy-Kheng
    Paluch, Shani Shimon
    Laitman, Yael
    Skytte, Anne-Bine
    Kruse, Torben A.
    Jensen, Uffe Birk
    Robson, Mark
    Gerdes, Anne-Marie
    Ejlertsen, Bent
    Foretova, Lenka
    Savage, Sharon A.
    Lesterm, Jenny
    Soucy, Penny
    Kuchenbaecker, Karoline B.
    Olswold, Curtis
    Cunningham, Julie M.
    Slager, Susan
    Pankratz, Vernon S.
    Dicks, Ed
    Lakhani, Sunil R.
    Couch, Fergus J.
    Hall, Per
    Monteiro, Alvaro N. A.
    Gayther, Simon A.
    Pharoah, Paul D. P.
    Reddel, Roger R.
    Goode, Ellen L.
    Greene, Mark H.
    Easton, Douglas F.
    Berchuck, Andrew
    Antoniou, Antonis C.
    Chenevix-Trench, Georgia
    Dunning, Alison M.
    Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer2013Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 4, s. 371-384Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.

  • 5. Bonn, Stefan
    et al.
    Zinzen, Robert P
    Girardot, Charles
    Gustafson, E Hilary
    Perez-Gonzalez, Alexis
    Delhomme, Nicolas
    Ghavi-Helm, Yad
    Wilczyński, Bartek
    Riddell, Andrew
    Furlong, Eileen E M
    Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development.2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chromatin modifications are associated with many aspects of gene expression, yet their role in cellular transitions during development remains elusive. Here, we use a new approach to obtain cell type-specific information on chromatin state and RNA polymerase II (Pol II) occupancy within the multicellular Drosophila melanogaster embryo. We directly assessed the relationship between chromatin modifications and the spatio-temporal activity of enhancers. Rather than having a unique chromatin state, active developmental enhancers show heterogeneous histone modifications and Pol II occupancy. Despite this complexity, combined chromatin signatures and Pol II presence are sufficient to predict enhancer activity de novo. Pol II recruitment is highly predictive of the timing of enhancer activity and seems dependent on the timing and location of transcription factor binding. Chromatin modifications typically demarcate large regulatory regions encompassing multiple enhancers, whereas local changes in nucleosome positioning and Pol II occupancy delineate single active enhancers. This cell type-specific view identifies dynamic enhancer usage, an essential step in deciphering developmental networks.

  • 6. Deloukas, Panos
    et al.
    Kanoni, Stavroula
    Willenborg, Christina
    Farrall, Martin
    Assimes, Themistocles L.
    Thompson, John R.
    Ingelsson, Erik
    Saleheen, Danish
    Erdmann, Jeanette
    Goldstein, Benjamin A.
    Stirrups, Kathleen
    Koenig, Inke R.
    Cazier, Jean-Baptiste
    Johansson, Asa
    Hall, Alistair S.
    Lee, Jong-Young
    Willer, Cristen J.
    Chambers, John C.
    Esko, Tonu
    Folkersen, Lasse
    Goel, Anuj
    Grundberg, Elin
    Havulinna, Aki S.
    Ho, Weang K.
    Hopewell, Jemma C.
    Eriksson, Niclas
    Kleber, Marcus E.
    Kristiansson, Kati
    Lundmark, Per
    Lyytikainen, Leo-Pekka
    Rafelt, Suzanne
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Strawbridge, Rona J.
    Thorleifsson, Gudmar
    Tikkanen, Emmi
    Van Zuydam, Natalie
    Voight, Benjamin F.
    Waite, Lindsay L.
    Zhang, Weihua
    Ziegler, Andreas
    Absher, Devin
    Altshuler, David
    Balmforth, Anthony J.
    Barroso, Ines
    Braund, Peter S.
    Burgdorf, Christof
    Claudi-Boehm, Simone
    Cox, David
    Dimitriou, Maria
    Do, Ron
    Doney, Alex S. F.
    El Mokhtari, NourEddine
    Eriksson, Per
    Fischer, Krista
    Fontanillas, Pierre
    Franco-Cereceda, Anders
    Gigante, Bruna
    Groop, Leif
    Gustafsson, Stefan
    Hager, Joerg
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Han, Bok-Ghee
    Hunt, Sarah E.
    Kang, Hyun M.
    Illig, Thomas
    Kessler, Thorsten
    Knowles, Joshua W.
    Kolovou, Genovefa
    Kuusisto, Johanna
    Langenberg, Claudia
    Langford, Cordelia
    Leander, Karin
    Lokki, Marja-Liisa
    Lundmark, Anders
    McCarthy, Mark I.
    Meisinger, Christa
    Melander, Olle
    Mihailov, Evelin
    Maouche, Seraya
    Morris, Andrew D.
    Mueller-Nurasyid, Martina
    Nikus, Kjell
    Peden, John F.
    Rayner, N. William
    Rasheed, Asif
    Rosinger, Silke
    Rubin, Diana
    Rumpf, Moritz P.
    Schaefer, Arne
    Sivananthan, Mohan
    Song, Ci
    Stewart, Alexandre F. R.
    Tan, Sian-Tsung
    Thorgeirsson, Gudmundur
    van der Schoot, C. Ellen
    Wagner, Peter J.
    Wells, George A.
    Wild, Philipp S.
    Yang, Tsun-Po
    Amouyel, Philippe
    Arveiler, Dominique
    Basart, Hanneke
    Boehnke, Michael
    Boerwinkle, Eric
    Brambilla, Paolo
    Cambien, Francois
    Cupples, Adrienne L.
    de Faire, Ulf
    Dehghan, Abbas
    Diemert, Patrick
    Epstein, Stephen E.
    Evans, Alun
    Ferrario, Marco M.
    Ferrieres, Jean
    Gauguier, Dominique
    Go, Alan S.
    Goodall, Alison H.
    Gudnason, Villi
    Hazen, Stanley L.
    Holm, Hilma
    Iribarren, Carlos
    Jang, Yangsoo
    Kahonen, Mika
    Kee, Frank
    Kim, Hyo-Soo
    Klopp, Norman
    Koenig, Wolfgang
    Kratzer, Wolfgang
    Kuulasmaa, Kari
    Laakso, Markku
    Laaksonen, Reijo
    Lee, Ji-Young
    Lind, Lars
    Ouwehand, Willem H.
    Parish, Sarah
    Park, Jeong E.
    Pedersen, Nancy L.
    Peters, Annette
    Quertermous, Thomas
    Rader, Daniel J.
    Salomaa, Veikko
    Schadt, Eric
    Shah, Svati H.
    Sinisalo, Juha
    Stark, Klaus
    Stefansson, Kari
    Tregouet, David-Alexandre
    Virtamo, Jarmo
    Wallentin, Lars
    Wareham, Nicholas
    Zimmermann, Martina E.
    Nieminen, Markku S.
    Hengstenberg, Christian
    Sandhu, Manjinder S.
    Pastinen, Tomi
    Syvanen, Ann-Christine
    Hovingh, G. Kees
    Dedoussis, George
    Franks, Paul W.
    Lehtimaki, Terho
    Metspalu, Andres
    Zalloua, Pierre A.
    Siegbahn, Agneta
    Schreiber, Stefan
    Ripatti, Samuli
    Blankenberg, Stefan S.
    Perola, Markus
    Clarke, Robert
    Boehm, Bernhard O.
    O'Donnell, Christopher
    Reilly, Muredach P.
    Maerz, Winfried
    Collins, Rory
    Kathiresan, Sekar
    Hamsten, Anders
    Kooner, Jaspal S.
    Thorsteinsdottir, Unnur
    Danesh, John
    Palmer, Colin N. A.
    Roberts, Robert
    Watkins, Hugh
    Schunkert, Heribert
    Samani, Nilesh J.
    Large-scale association analysis identifies new risk loci for coronary artery disease2013Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 1, s. 25-U52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

  • 7. Deng, Min
    et al.
    Wei, Ling
    Zuo, Xianbo
    Tian, Yanghua
    Xie, Fei
    Hu, Panpan
    Zhu, Chunyan
    Yu, Fengqiong
    Meng, Yu
    Wang, Honghao
    Zhang, Fangfang
    Ma, Huijuan
    Ye, Rong
    Cheng, Huaidong
    Du, Jing
    Dong, Wenwen
    Zhou, Shanshan
    Wang, Changqing
    Wang, Yu
    Wang, Jingye
    Chen, Xianwen
    Sun, Zhongwu
    Zhou, Nong
    Jiang, Yubao
    Liu, Xiuxiu
    Li, Xiaogang
    Zhang, Nan
    Liu, Na
    Guan, Yingjun
    Han, Yongsheng
    Han, Yongzhu
    Lv, Xinyi
    Fu, Yu
    Yu, Hui
    Xi, Chunhua
    Xie, Dandan
    Zhao, Qiyuan
    Xie, Peng
    Wang, Xin
    Zhang, Zhijun
    Shen, Lu
    Cui, Yong
    Yin, Xianyong
    Cheng, Hui
    Liang, Bo
    Zheng, Xiaodong
    Lee, Tatia M. C.
    Chen, Gang
    Zhou, Fusheng
    Veldink, Jan H.
    Robberecht, Wim
    Landers, John E.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Al-Chalabi, Ammar
    Shaw, Chris
    Liu, Chunfeng
    Tang, Beisha
    Xiao, Shangxi
    Robertson, Janice
    Zhang, Fengyu
    van den Berg, Leonard H.
    Sun, Liangdan
    Liu, Jianjun
    Yang, Sen
    Ju, Xiaodong
    Wang, Kai
    Zhang, Xuejun
    Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis2013Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 6, s. 697-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.

  • 8. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Kanoni, Stavroula
    Ganna, Andrea
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Asa
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Lunds universitet.
    Sidore, Carlo
    Song, Ci
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lunds universitet, Harvard University.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 11, s. 1345-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 9. Dobbins, Sara E.
    et al.
    Broderick, Peter
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Feychting, Maria
    Johansen, Christoffer
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Schramm, Johannes
    Olver, Bianca
    Lloyd, Amy
    Ma, Yussanne P.
    Hosking, Fay J.
    Lönn, Stefan
    Ahlbom, Anders
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Schoemaker, Minouk J.
    Hepworth, Sarah J.
    Hoffmann, Per
    Muehleisen, Thomas W.
    Noethen, Markus M.
    Moebus, Susanne
    Eisele, Lewin
    Kosteljanetz, Michael
    Muir, Kenneth
    Swerdlow, Anthony
    Simon, Matthias
    Houlston, Richard S.
    Common variation at 10p12.31 near MLLT10 influences meningioma risk2011Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 43, nr 9, s. 825-827Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.

  • 10. Dupuis, Josée
    et al.
    Langenberg, Claudia
    Prokopenko, Inga
    Saxena, Richa
    Soranzo, Nicole
    Jackson, Anne U
    Wheeler, Eleanor
    Glazer, Nicole L
    Bouatia-Naji, Nabila
    Gloyn, Anna L
    Lindgren, Cecilia M
    Mägi, Reedik
    Morris, Andrew P
    Randall, Joshua
    Johnson, Toby
    Elliott, Paul
    Rybin, Denis
    Thorleifsson, Gudmar
    Steinthorsdottir, Valgerdur
    Henneman, Peter
    Grallert, Harald
    Dehghan, Abbas
    Hottenga, Jouke Jan
    Franklin, Christopher S
    Navarro, Pau
    Song, Kijoung
    Goel, Anuj
    Perry, John R B
    Egan, Josephine M
    Lajunen, Taina
    Grarup, Niels
    Sparsø, Thomas
    Doney, Alex
    Voight, Benjamin F
    Stringham, Heather M
    Li, Man
    Kanoni, Stavroula
    Shrader, Peter
    Cavalcanti-Proença, Christine
    Kumari, Meena
    Qi, Lu
    Timpson, Nicholas J
    Gieger, Christian
    Zabena, Carina
    Rocheleau, Ghislain
    Ingelsson, Erik
    An, Ping
    O'Connell, Jeffrey
    Luan, Jian'an
    Elliott, Amanda
    McCarroll, Steven A
    Payne, Felicity
    Roccasecca, Rosa Maria
    Pattou, François
    Sethupathy, Praveen
    Ardlie, Kristin
    Ariyurek, Yavuz
    Balkau, Beverley
    Barter, Philip
    Beilby, John P
    Ben-Shlomo, Yoav
    Benediktsson, Rafn
    Bennett, Amanda J
    Bergmann, Sven
    Bochud, Murielle
    Boerwinkle, Eric
    Bonnefond, Amélie
    Bonnycastle, Lori L
    Borch-Johnsen, Knut
    Böttcher, Yvonne
    Brunner, Eric
    Bumpstead, Suzannah J
    Charpentier, Guillaume
    Chen, Yii-Der Ida
    Chines, Peter
    Clarke, Robert
    Coin, Lachlan J M
    Cooper, Matthew N
    Cornelis, Marilyn
    Crawford, Gabe
    Crisponi, Laura
    Day, Ian N M
    de Geus, Eco J C
    Delplanque, Jerome
    Dina, Christian
    Erdos, Michael R
    Fedson, Annette C
    Fischer-Rosinsky, Antje
    Forouhi, Nita G
    Fox, Caroline S
    Frants, Rune
    Franzosi, Maria Grazia
    Galan, Pilar
    Goodarzi, Mark O
    Graessler, Jürgen
    Groves, Christopher J
    Grundy, Scott
    Gwilliam, Rhian
    Gyllensten, Ulf
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hadjadj, Samy
    Hammond, Naomi
    Han, Xijing
    Hartikainen, Anna-Liisa
    Hassanali, Neelam
    Hayward, Caroline
    Heath, Simon C
    Hercberg, Serge
    Herder, Christian
    Hicks, Andrew A
    Hillman, David R
    Hingorani, Aroon D
    Hofman, Albert
    Hui, Jennie
    Hung, Joe
    Isomaa, Bo
    Johnson, Paul R V
    Jørgensen, Torben
    Jula, Antti
    Kaakinen, Marika
    Kaprio, Jaakko
    Kesaniemi, Y Antero
    Kivimaki, Mika
    Knight, Beatrice
    Koskinen, Seppo
    Kovacs, Peter
    Kyvik, Kirsten Ohm
    Lathrop, G Mark
    Lawlor, Debbie A
    Le Bacquer, Olivier
    Lecoeur, Cécile
    Li, Yun
    Lyssenko, Valeriya
    Mahley, Robert
    Mangino, Massimo
    Manning, Alisa K
    Martínez-Larrad, María Teresa
    McAteer, Jarred B
    McCulloch, Laura J
    McPherson, Ruth
    Meisinger, Christa
    Melzer, David
    Meyre, David
    Mitchell, Braxton D
    Morken, Mario A
    Mukherjee, Sutapa
    Naitza, Silvia
    Narisu, Narisu
    Neville, Matthew J
    Oostra, Ben A
    Orrù, Marco
    Pakyz, Ruth
    Palmer, Colin N A
    Paolisso, Giuseppe
    Pattaro, Cristian
    Pearson, Daniel
    Peden, John F
    Pedersen, Nancy L
    Perola, Markus
    Pfeiffer, Andreas F H
    Pichler, Irene
    Polasek, Ozren
    Posthuma, Danielle
    Potter, Simon C
    Pouta, Anneli
    Province, Michael A
    Psaty, Bruce M
    Rathmann, Wolfgang
    Rayner, Nigel W
    Rice, Kenneth
    Ripatti, Samuli
    Rivadeneira, Fernando
    Roden, Michael
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandbaek, Annelli
    Sandhu, Manjinder
    Sanna, Serena
    Sayer, Avan Aihie
    Scheet, Paul
    Scott, Laura J
    Seedorf, Udo
    Sharp, Stephen J
    Shields, Beverley
    Sigurethsson, Gunnar
    Sijbrands, Eric J G
    Silveira, Angela
    Simpson, Laila
    Singleton, Andrew
    Smith, Nicholas L
    Sovio, Ulla
    Swift, Amy
    Syddall, Holly
    Syvänen, Ann-Christine
    Tanaka, Toshiko
    Thorand, Barbara
    Tichet, Jean
    Tönjes, Anke
    Tuomi, Tiinamaija
    Uitterlinden, André G
    van Dijk, Ko Willems
    van Hoek, Mandy
    Varma, Dhiraj
    Visvikis-Siest, Sophie
    Vitart, Veronique
    Vogelzangs, Nicole
    Waeber, Gérard
    Wagner, Peter J
    Walley, Andrew
    Walters, G Bragi
    Ward, Kim L
    Watkins, Hugh
    Weedon, Michael N
    Wild, Sarah H
    Willemsen, Gonneke
    Witteman, Jaqueline C M
    Yarnell, John W G
    Zeggini, Eleftheria
    Zelenika, Diana
    Zethelius, Björn
    Zhai, Guangju
    Zhao, Jing Hua
    Zillikens, M Carola
    Borecki, Ingrid B
    Loos, Ruth J F
    Meneton, Pierre
    Magnusson, Patrik K E
    Nathan, David M
    Williams, Gordon H
    Hattersley, Andrew T
    Silander, Kaisa
    Salomaa, Veikko
    Smith, George Davey
    Bornstein, Stefan R
    Schwarz, Peter
    Spranger, Joachim
    Karpe, Fredrik
    Shuldiner, Alan R
    Cooper, Cyrus
    Dedoussis, George V
    Serrano-Ríos, Manuel
    Morris, Andrew D
    Lind, Lars
    Palmer, Lyle J
    Hu, Frank B
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ebrahim, Shah
    Marmot, Michael
    Kao, W H Linda
    Pankow, James S
    Sampson, Michael J
    Kuusisto, Johanna
    Laakso, Markku
    Hansen, Torben
    Pedersen, Oluf
    Pramstaller, Peter Paul
    Wichmann, H Erich
    Illig, Thomas
    Rudan, Igor
    Wright, Alan F
    Stumvoll, Michael
    Campbell, Harry
    Wilson, James F
    Bergman, Richard N
    Buchanan, Thomas A
    Collins, Francis S
    Mohlke, Karen L
    Tuomilehto, Jaakko
    Valle, Timo T
    Altshuler, David
    Rotter, Jerome I
    Siscovick, David S
    Penninx, Brenda W J H
    Boomsma, Dorret I
    Deloukas, Panos
    Spector, Timothy D
    Frayling, Timothy M
    Ferrucci, Luigi
    Kong, Augustine
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    van Duijn, Cornelia M
    Aulchenko, Yurii S
    Cao, Antonio
    Scuteri, Angelo
    Schlessinger, David
    Uda, Manuela
    Ruokonen, Aimo
    Jarvelin, Marjo-Riitta
    Waterworth, Dawn M
    Vollenweider, Peter
    Peltonen, Leena
    Mooser, Vincent
    Abecasis, Goncalo R
    Wareham, Nicholas J
    Sladek, Robert
    Froguel, Philippe
    Watanabe, Richard M
    Meigs, James B
    Groop, Leif
    Boehnke, Michael
    McCarthy, Mark I
    Florez, Jose C
    Barroso, Inês
    New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk2010Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, nr 2, s. 105-116Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

  • 11. Ehret, Georg B.
    et al.
    Ferreira, Teresa
    Chasman, Daniel I.
    Jackson, Anne U.
    Schmidt, Ellen M.
    Johnson, Toby
    Thorleifsson, Gudmar
    Luan, Jian'an
    Donnelly, Louise A.
    Kanoni, Stavroula
    Petersen, Ann -Kristin
    Pihurl, Vasyl
    Strawbridge, Rona J.
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Hughes, Maria F.
    Meirelles, Osorio
    Kaakinen, Marika
    Bouatia-Naji, Nabila
    Kristiansson, Kati
    Shah, Sonia
    Kleber, Marcus E.
    Guo, Xiuqing
    Lyytikainen, Leo-Pekka
    Fava, Cristiano
    Eriksson, Nidas
    Nolte, Ilja M.
    Magnusson, Patrik K.
    Salfati, Elias L.
    Rallidis, Loukianos S.
    Theusch, Elizabeth
    Smith, Andrew J. P.
    Folkersen, Lasse
    Witkowska, Kate
    Pers, Tune H.
    Joehanes, Roby
    Kim, Stuart K.
    Lataniotis, Lazaros
    Jansen, Rick
    Johnson, Andrew D.
    Warren, Helen
    Kim, Young Jin
    Zhao, Wei
    Wu, Ying
    Tayo, Bamidele O.
    Bochud, Murielle
    Absher, Devin
    Adair, Linda S.
    Amin, Najaf
    Arkingl, Dan E.
    Axelsson, Tomas
    Baldassarre, Damian
    Balkau, Beverley
    Bandinelli, Stefania
    Barnes, Michael R.
    Barroso, Ines
    Bevan, Stephen
    Bis, Joshua C.
    Bjornsdottir, Gyda
    Boehnke, Michael
    Boerwinkle, Eric
    Bonnycastle, Lori L.
    Boomsma, Dorret I.
    Bornstein, Stefan R.
    Brown, Morris J.
    Burnier, Michel
    Cabrera, Claudia P.
    Chambers, John C.
    Chang, I-Shou
    Cheng, Ching-Yu
    Chines, Peter S.
    Chung, Ren-Hua
    Collins, Francis S.
    Connell, John M.
    Doring, Angela
    Dallongeville, Jean
    Danesh, John
    de Faire, Ulf
    Delgado, Graciela
    Dominiczak, Anna F.
    Doney, Alex S. F.
    Drenos, Fotios
    Edkins, Sarah
    Eicher, John D.
    Elosua, Roberto
    Enroth, Stefan
    Erdmann, Jeanette
    Eriksson, Per
    Esko, Tonu
    Evangelou, Evangelos
    Evans, Alun
    Fai, Tove
    Farra, Martin
    Felixl, Janine F.
    Ferrieres, Jean
    Ferrucci, Luigi
    Fornage, Myriam
    Forrester, Terrence
    Franceschinil, Nora
    Franco, Oscar H.
    Franco-Cereceda, Anders
    Fraser, Ross M.
    Ganesh, Santhi K.
    Gao, He
    Gertow, Karl
    Gianfagna, Francesco
    Gigante, Bruna
    Giulianini, Franco
    Goe, Anuj
    Goodall, Alison H.
    Goodarzi, Mark
    Gorski, Mathias
    Grassler, Jurgen
    Groves, Christopher J.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hartikainen, Anna-Liisa
    Hassinen, Maija
    Havulinna, Aki S.
    Hayward, Caroline
    Hercberg, Serge
    Herzig, Karl-Heinz
    Hicks, Andrew A.
    Hingorani, Aroon D.
    Hirschhorn, Joel N.
    Hofmanl, Albert
    Holmen, Jostein
    Holmen, Oddgeir Lingaas
    Hottenga, Jouke-Jan
    Howard, Phil
    Hsiung, Chao A.
    Hunt, Steven C.
    Ikram, M. Arfan
    Illig, Thomas
    Iribarren, Carlos
    Jensen, Richard A.
    Kahonen, Mika
    Kang, Hyun Min
    Kathiresan, Sekar
    Keating, Brendan J.
    Khaw, Kay-Tee
    Kim, Yun Kyoung
    Kim, Eric
    Kivimaki, Mika
    Klopp, Norman
    Kolovou, Genovefa
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kosova, Gulum
    Krauss, Ronald M.
    Kuh, Diana
    Kutalik, Zoltan
    Kuusisto, Johanna
    Kvaloy, Kirsti
    Lakka, Timo A.
    Lee, Nanette R.
    Lee, I-Te
    Lee, Wen-Jane
    Levy, Daniel
    Li, Xiaohui
    Liang, Kae-Woei
    Lin, Honghuang
    Lin, Li
    Lindstrom, Jaana
    Lobbens, Stephane
    Mannisto, Satu
    Muller, Gabriele
    Muller-Nurasyid, Martina
    Mach, Francois
    Markus, Hugh S.
    Marouli, Eirini
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Menni, Cristina
    Metspalu, Andres
    Mijatovic, Vladan
    Moilanen, Leena
    Montasser, May E.
    Morris, Andrew D.
    Morrison, Alanna C.
    Mulas, Antonella
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nikus, Kjell
    O'Donnell, Christopher J.
    O'Reilly, Paul F.
    Ong, Ken K.
    Paccaud, Fred
    Palmer, Cameron D.
    Parsa, Afshin
    Pedersen, Nancy L.
    Penninx, Brenda W.
    Perola, Markus
    Peters, Annette
    Poulter, Neil
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rao, Dabeeru C.
    Rasheed, Asif
    Rayner, N. William
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rettig, Rainer
    Rice, Kenneth M.
    Roberts, Robert
    Rose, Lynda M.
    Rossouw, Jacques
    Samani, Nilesh J.
    Sanna, Serena
    Saramies, Jouko
    Schunkert, Heribert
    Sebert, Sylvain
    Sheu, Wayne H-H
    Shin, Young-Ah
    Sim, Xueling
    Smit, Johannes H.
    Smith, Albert V.
    Sosa, Maria X.
    Spector, Tim D.
    Stancakova, Alena
    Stanton, Alice V.
    Stirrups, Kathleen E.
    Stringham, Heather M.
    Sundstrom, Johan
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tai, E-Shyong
    Tanaka, Toshiko
    Tarasov, Kirill V.
    Teumer, Alexander
    Thorsteinsdottir, Unnur
    Tobin, Martin D.
    Tremoli, Elena
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Vaez, Ahmad
    Vaidya, Dhananjay
    van Duijn, Cornelia M.
    van Iperen, Erik P. A.
    Vasan, Ramachandran S.
    Verwoert, Germaine C.
    Virtamo, Jarmo
    Vitart, Veronique
    Voight, Benjamin F.
    Vollenweider, Peter
    Wagner, Aline
    Wain, Louise V.
    Wareham, Nicholas J.
    Watldns, Hugh
    Weder, Alan B.
    Westra, Harm Jan
    Wilks, Rainford
    Wilsgaard, Tom
    Wilson, James F.
    Wong, Tien Y.
    Yang, Tsun-Po
    Yao, Jie
    Yengo, Loic
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Xiaofeng
    Bovet, Pascal
    Cooper, Richard S.
    Mohlke, Karen L.
    Saleheen, Danish
    Lee, Jong-Young
    Elliott, Paul
    Gierman, Hinco J.
    Willer, Cristen J.
    Franke, Lude
    Hovingh, G. Kees
    Taylor, Kent D.
    Dedoussis, George
    Sever, Peter
    Wong, Andrew
    Lind, Lars
    Assimes, Themistocles L.
    Njolstad, Inger
    Schwarz, Peter E. H.
    Langenberg, Claudia
    Snieder, Harold
    Caulfield, Mark J.
    Melander, E.
    Laakso, Markku
    Saltevo, Juha
    Rauramaa, Rainer
    Tuomilehto, Jaakko
    Ingelsson, Erik
    Lehtimaki, Terho
    Hveem, Kristian
    Palmas, Walter
    Marz, Winfried
    Kumar, Meena
    Salomaa, Veikko
    Chen, Yii-Der I.
    Rotter, Jerome I.
    Froguel, Philippe
    Jarvelin, Marjo-Riitta
    Lakatta, Edward G.
    Kuulasmaa, Kari
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
    Hamsten, Anders
    Wichmann, H-Erich
    Palmer, Colin N. A.
    Stefansson, Kari
    Ridker, Paul M.
    Loos, Ruth J. F.
    Chalcravarti, Aravinda
    Deloukas, Panos
    Morris, Andrew P.
    Newton-Cheh, Christopher
    Munroe, Patricia B.
    The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 10, s. 1171-1184Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

  • 12. Estrada, Karol
    et al.
    Styrkarsdottir, Unnur
    Evangelou, Evangelos
    Hsu, Yi-Hsiang
    Duncan, Emma L
    Ntzani, Evangelia E
    Oei, Ling
    Albagha, Omar ME
    Amin, Najaf
    Kemp, John P
    Koller, Daniel L
    Li, Guo
    Liu, Ching-Ti
    Minster, Ryan L
    Moayyeri, Alireza
    Vandenput, Liesbeth
    Willner, Dana
    Xiao, Su-Mei
    Yerges-Armstrong, Laura M
    Zheng, Hou-Feng
    Alonso, Nerea
    Eriksson, Joel
    Kammerer, Candace M
    Kaptoge, Stephen K
    Leo, Paul J
    Thorleifsson, Gudmar
    Wilson, Scott G
    Wilson, James F
    Aalto, Ville
    Alen, Markku
    Aragaki, Aaron K
    Aspelund, Thor
    Center, Jacqueline R
    Dailiana, Zoe
    Duggan, David J
    Garcia, Melissa
    Garcia-Giralt, Natàlia
    Giroux, Sylvie
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Khusainova, Rita
    Kim, Ghi Su
    Kooperberg, Charles
    Koromila, Theodora
    Kruk, Marcin
    Laaksonen, Marika
    Lacroix, Andrea Z
    Lee, Seung Hun
    Leung, Ping C
    Lewis, Joshua R
    Masi, Laura
    Mencej-Bedrac, Simona
    Nguyen, Tuan V
    Nogues, Xavier
    Patel, Millan S
    Prezelj, Janez
    Rose, Lynda M
    Scollen, Serena
    Siggeirsdottir, Kristin
    Smith, Albert V
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Trompet, Stella
    Trummer, Olivia
    van Schoor, Natasja M
    Woo, Jean
    Zhu, Kun
    Balcells, Susana
    Brandi, Maria Luisa
    Buckley, Brendan M
    Cheng, Sulin
    Christiansen, Claus
    Cooper, Cyrus
    Dedoussis, George
    Ford, Ian
    Frost, Morten
    Goltzman, David
    González-Macías, Jesús
    Kähönen, Mika
    Karlsson, Magnus
    Khusnutdinova, Elza
    Koh, Jung-Min
    Kollia, Panagoula
    Langdahl, Bente Lomholt
    Leslie, William D
    Lips, Paul
    Ljunggren, Osten
    Lorenc, Roman S
    Marc, Janja
    Mellström, Dan
    Obermayer-Pietsch, Barbara
    Olmos, José M
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Reid, David M
    Riancho, José A
    Ridker, Paul M
    Rousseau, François
    Lagboom, P Eline S
    Tang, Nelson LS
    Urreizti, Roser
    Van Hul, Wim
    Viikari, Jorma
    Zarrabeitia, María T
    Aulchenko, Yurii S
    Castano-Betancourt, Martha
    Grundberg, Elin
    Herrera, Lizbeth
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Kwan, Tony
    Li, Rui
    Luben, Robert
    Medina-Gómez, Carolina
    Th Palsson, Stefan
    Reppe, Sjur
    Rotter, Jerome I
    Sigurdsson, Gunnar
    van Meurs, Joyce BJ
    Verlaan, Dominique
    Williams, Frances MK
    Wood, Andrew R
    Zhou, Yanhua
    Gautvik, Kaare M
    Pastinen, Tomi
    Raychaudhuri, Soumya
    Cauley, Jane A
    Chasman, Daniel I
    Clark, Graeme R
    Cummings, Steven R
    Danoy, Patrick
    Dennison, Elaine M
    Eastell, Richard
    Eisman, John A
    Gudnason, Vilmundur
    Hofman, Albert
    Jackson, Rebecca D
    Jones, Graeme
    Jukema, J Wouter
    Khaw, Kay-Tee
    Lehtimäki, Terho
    Liu, Yongmei
    Lorentzon, Mattias
    McCloskey, Eugene
    Mitchell, Braxton D
    Nandakumar, Kannabiran
    Nicholson, Geoffrey C
    Oostra, Ben A
    Peacock, Munro
    Pols, Huibert AP
    Prince, Richard L
    Raitakari, Olli
    Reid, Ian R
    Robbins, John
    Sambrook, Philip N
    Sham, Pak Chung
    Shuldiner, Alan R
    Tylavsky, Frances A
    van Duijn, Cornelia M
    Wareham, Nick J
    Cupples, L Adrienne
    Econs, Michael J
    Evans, David M
    Harris, Tamara B
    Kung, Annie Wai Chee
    Psaty, Bruce M
    Reeve, Jonathan
    Spector, Timothy D
    Streeten, Elizabeth A
    Zillikens, M Carola
    Thorsteinsdottir, Unnur
    Ohlsson, Claes
    Karasik, David
    Richards, J Brent
    Brown, Matthew A
    Stefansson, Kari
    Uitterlinden, André G
    Ralston, Stuart H
    Ioannidis, John PA
    Kiel, Douglas P
    Rivadeneira, Fernando
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, s. 491-501Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

  • 13. Eyre, Steve
    et al.
    Bowes, John
    Diogo, Dorothee
    Lee, Annette
    Barton, Anne
    Martin, Paul
    Zhernakova, Alexandra
    Stahl, Eli
    Viatte, Sebastien
    McAllister, Kate
    Amos, Christopher I.
    Padyukov, Leonid
    Toes, Rene E. M.
    Huizinga, Tom W. J.
    Wijmenga, Cisca
    Trynka, Gosia
    Franke, Lude
    Westra, Harm-Jan
    Alfredsson, Lars
    Hu, Xinli
    Sandor, Cynthia
    de Bakker, Paul I. W.
    Davila, Sonia
    Khor, Chiea Chuen
    Heng, Khai Koon
    Andrews, Robert
    Edkins, Sarah
    Hunt, Sarah E.
    Langford, Cordelia
    Symmons, Deborah
    Concannon, Pat
    Onengut-Gumuscu, Suna
    Rich, Stephen S.
    Deloukas, Panos
    Gonzalez-Gay, Miguel A.
    Rodriguez-Rodriguez, Luis
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Martin, Javier
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Plenge, Robert M.
    Raychaudhuri, Soumya
    Klareskog, Lars
    Gregersen, Peter K.
    Worthington, Jane
    High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 12, s. 1336-1340Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

  • 14. Gaulton, Kyle J.
    et al.
    Ferreira, Teresa
    Lee, Yeji
    Raimondo, Anne
    Maegi, Reedik
    Reschen, Michael E.
    Mahajan, Anubha
    Locke, Adam
    Rayner, N. William
    Robertson, Neil
    Scott, Robert A.
    Prokopenko, Inga
    Scott, Laura J.
    Green, Todd
    Sparso, Thomas
    Thuillier, Dorothee
    Yengo, Loic
    Grallert, Harald
    Wahl, Simone
    Franberg, Mattias
    Strawbridge, Rona J.
    Kestler, Hans
    Chheda, Himanshu
    Eisele, Lewin
    Gustafsson, Stefan
    Steinthorsdottir, Valgerdur
    Thorleifsson, Gudmar
    Qi, Lu
    Karssen, Lennart C.
    van Leeuwen, Elisabeth M.
    Willems, Sara M.
    Li, Man
    Chen, Han
    Fuchsberger, Christian
    Kwan, Phoenix
    Ma, Clement
    Linderman, Michael
    Lu, Yingchang
    Thomsen, Soren K.
    Rundle, Jana K.
    Beer, Nicola L.
    van de Bunt, Martijn
    Chalisey, Anil
    Kang, Hyun Min
    Voight, Benjamin F.
    Abecasis, Goncalo R.
    Almgren, Peter
    Baldassarre, Damiano
    Balkau, Beverley
    Benediktsson, Rafn
    Blueher, Matthias
    Boeing, Heiner
    Bonnycastle, Lori L.
    Bottinger, Erwin P.
    Burtt, Noel P.
    Carey, Jason
    Charpentier, Guillaume
    Chines, Peter S.
    Cornelis, Marilyn C.
    Couper, David J.
    Crenshaw, Andrew T.
    van Dam, Rob M.
    Doney, Alex S. F.
    Dorkhan, Mozhgan
    Edkins, Sarah
    Eriksson, Johan G.
    Esko, Tonu
    Eury, Elodie
    Fadista, Joao
    Flannick, Jason
    Fontanillas, Pierre
    Fox, Caroline
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA; Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden; Department of Clinical Sciences, Lund University, Malmö, Sweden..
    Gertow, Karl
    Gieger, Christian
    Gigante, Bruna
    Gottesman, Omri
    Grant, George B.
    Grarup, Niels
    Groves, Christopher J.
    Hassinen, Maija
    Have, Christian T.
    Herder, Christian
    Holmen, Oddgeir L.
    Hreidarsson, Astradur B.
    Humphries, Steve E.
    Hunter, David J.
    Jackson, Anne U.
    Jonsson, Anna
    Jorgensen, Marit E.
    Jorgensen, Torben
    Kao, Wen-Hong L.
    Kerrison, Nicola D.
    Kinnunen, Leena
    Klopp, Norman
    Kong, Augustine
    Kovacs, Peter
    Kraft, Peter
    Kravic, Jasmina
    Langford, Cordelia
    Leander, Karin
    Liang, Liming
    Lichtner, Peter
    Lindgren, Cecilia M.
    Lindholm, Eero
    Linneberg, Allan
    Liu, Ching-Ti
    Lobbens, Stephane
    Luan, Jian'an
    Lyssenko, Valeriya
    Mannisto, Satu
    McLeod, Olga
    Meyer, Julia
    Mihailov, Evelin
    Mirza, Ghazala
    Muehleisen, Thomas W.
    Mueller-Nurasyid, Martina
    Navarro, Carmen
    Noethen, Markus M.
    Oskolkov, Nikolay N.
    Owen, Katharine R.
    Palli, Domenico
    Pechlivanis, Sonali
    Peltonen, Leena
    Perry, John R. B.
    Platou, Carl G. P.
    Roden, Michael
    Ruderfer, Douglas
    Rybin, Denis
    van der Schouw, Yvonne T.
    Sennblad, Bengt
    Sigurdsson, Gunnar
    Stancakova, Alena
    Steinbach, Gerald
    Storm, Petter
    Strauch, Konstantin
    Stringham, Heather M.
    Sun, Qi
    Thorand, Barbara
    Tikkanen, Emmi
    Tonjes, Anke
    Trakalo, Joseph
    Tremoli, Elena
    Tuomi, Tiinamaija
    Wennauer, Roman
    Wiltshire, Steven
    Wood, Andrew R.
    Zeggini, Eleftheria
    Dunham, Ian
    Birney, Ewan
    Pasquali, Lorenzo
    Ferrer, Jorge
    Loos, Ruth J. F.
    Dupuis, Josee
    Florez, Jose C.
    Boerwinkle, Eric
    Pankow, James S.
    van Duijn, Cornelia
    Sijbrands, Eric
    Meigs, James B.
    Hu, Frank B.
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    Lakka, Timo A.
    Rauramaa, Rainer
    Stumvoll, Michael
    Pedersen, Nancy L.
    Lind, Lars
    Keinanen-Kiukaanniemi, Sirkka M.
    Korpi-Hyovalti, Eeva
    Saaristo, Timo E.
    Saltevo, Juha
    Kuusisto, Johanna
    Laakso, Markku
    Metspalu, Andres
    Erbel, Raimund
    Joecke, Karl-Heinz
    Moebus, Susanne
    Ripatti, Samuli
    Salomaa, Veikko
    Ingelsson, Erik
    Boehm, Bernhard O.
    Bergman, Richard N.
    Collins, Francis S.
    Mohlke, Karen L.
    Koistinen, Heikki
    Tuomilehto, Jaakko
    Hveem, Kristian
    Njolstad, Inger
    Deloukas, Panagiotis
    Donnelly, Peter J.
    Frayling, Timothy M.
    Hattersley, Andrew T.
    de Faire, Ulf
    Hamsten, Anders
    Illig, Thomas
    Peters, Annette
    Cauchi, Stephane
    Sladek, Rob
    Froguel, Philippe
    Hansen, Torben
    Pedersen, Oluf
    Morris, Andrew D.
    Palmer, Collin N. A.
    Kathiresan, Sekar
    Melander, Olle
    Nilsson, Peter M.
    Groop, Leif C.
    Barroso, Ines
    Langenberg, Claudia
    Wareham, Nicholas J.
    O'Callaghan, Christopher A.
    Gloyn, Anna L.
    Altshuler, David
    Boehnke, Michael
    Teslovich, Tanya M.
    McCarthy, Mark I.
    Morris, Andrew P.
    Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 12, s. 1415-1425Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

  • 15. Han, Buhm
    et al.
    Pouget, Jennie G.
    Slowikowski, Kamil
    Stahl, Eli
    Lee, Cue Hyunkyu
    Diogo, Dorothee
    Hu, Xinli
    Park, Yu Rang
    Kim, Eunji
    Gregersen, Peter K.
    Dahlqvist, Solbritt Rantapää
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Worthington, Jane
    Martin, Javier
    Eyre, Steve
    Klareskog, Lars
    Huizinga, Tom
    Chen, Wei-Min
    Onengut-Gumuscu, Suna
    Rich, Stephen S.
    Wray, Naomi R.
    Raychaudhuri, Soumya
    A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 7, s. 803-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is growing evidence of shared risk alleles for complex traits (pleiotropy), including autoimmune and neuropsychiatric diseases. This might be due to sharing among all individuals (whole-group pleiotropy) or a subset of individuals in a genetically heterogeneous cohort (subgroup heterogeneity). Here we describe the use of a well-powered statistic, BUHMBOX, to distinguish between those two situations using genotype data. We observed a shared genetic basis for 11 autoimmune diseases and type 1 diabetes (T1D; P < 1 x 10(-4)) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P < 1 x 10(-3)). This sharing was not explained by subgroup heterogeneity (corrected P-BUHMBOX > 0.2; 6,670 T1D cases and 7,279 RA cases). Genetic sharing between seronegative and seropostive RA (P < 1 x 10(-9)) had significant evidence of subgroup heterogeneity, suggesting a subgroup of seropositive-like cases within seronegative cases (P-BUHMBOX = 0.008; 2,406 seronegative RA cases). We also observed a shared genetic basis for major depressive disorder (MDD) and schizophrenia (P < 1 x 10(-4)) that was not explained by subgroup heterogeneity (P-BUHMBOX = 0.28; 9,238 MDD cases).

  • 16. Huckins, Laura M.
    et al.
    Dobbyn, Amanda
    Ruderfer, Douglas M.
    Hoffman, Gabriel
    Wang, Weiqing
    Pardinas, Antonio F.
    Rajagopal, Veera M.
    Als, Thomas D.
    Nguyen, Hoang T.
    Girdhar, Kiran
    Boocock, James
    Roussos, Panos
    Fromer, Menachem
    Kramer, Robin
    Domenici, Enrico
    Gamazon, Eric R.
    Purcell, Shaun
    Demontis, Ditte
    Borglum, Anders D.
    Walters, James T. R.
    O'Donovan, Michael C.
    Sullivan, Patrick
    Owen, Michael J.
    Devlin, Bernie
    Sieberts, Solveig K.
    Cox, Nancy J.
    Im, Hae Kyung
    Sklar, Pamela
    Stahl, Eli A.
    Johnson, Jessica S.
    Shah, Hardik R.
    Klein, Lambertus L.
    Dang, Kristen K.
    Logsdon, Benjamin A.
    Mahajan, Milind C.
    Mangravite, Lara M.
    Toyoshiba, Hiroyoshi
    Gur, Raquel E.
    Hahn, Chang-Gyu
    Schadt, Eric
    Lewis, David A.
    Haroutunian, Vahram
    Peters, Mette A.
    Lipska, Barbara K.
    Buxbaum, Joseph D.
    Hirai, Keisuke
    Perumal, Thanneer M.
    Essioux, Laurent
    Rajagopal, Veera Manikandan
    Mattheisen, Manuel
    Grove, Jakob
    Werge, Thomas
    Mortensen, Preben Bo
    Pedersen, Carsten Bocker
    Agerbo, Esben
    Pedersen, Marianne Giortz
    Mors, Ole
    Nordentoft, Merete
    Hougaard, David M.
    Bybjerg-Grauholm, Jonas
    Baekvad-Hansen, Marie
    Hansen, Christine Soholm
    Ripke, Stephan
    Neale, Benjamin M.
    Corvin, Aiden
    Farh, Kai-How
    Holmans, Peter A.
    Lee, Phil
    Bulik-Sullivan, Brendan
    Collier, David A.
    Huang, Hailiang
    Pers, Tune H.
    Agartz, Ingrid
    Albus, Margot
    Alexander, Madeline
    Amin, Farooq
    Bacanu, Silviu A.
    Begemann, Martin
    Belliveau, Richard A., Jr.
    Bene, Judit
    Bergen, Sarah E.
    Bevilacqua, Elizabeth
    Bigdeli, Tim B.
    Black, Donald W.
    Bruggeman, Richard
    Buccola, Nancy G.
    Buckner, Randy L.
    Byerley, William
    Cahn, Wiepke
    Cai, Guiqing
    Campion, Dominique
    Cantor, Rita M.
    Carr, Vaughan J.
    Carrera, Noa
    Catts, Stanley, V
    Chambert, Kimberly D.
    Chan, Raymond C. K.
    Chen, Ronald Y. L.
    Chen, Eric Y. H.
    Cheng, Wei
    Cheung, Eric F. C.
    Chong, Siow Ann
    Cloninger, C. Robert
    Cohen, David
    Cohen, Nadine
    Cormican, Paul
    Craddock, Nick
    Crowley, James J.
    Curtis, David
    Davidson, Michael
    Davis, Kenneth L.
    Degenhardt, Franziska
    Del Favero, Jurgen
    Dikeos, Dimitris
    Dinan, Timothy
    Djurovic, Srdjan
    Donohoe, Gary
    Drapeau, Elodie
    Duan, Jubao
    Dudbridge, Frank
    Durmishi, Naser
    Eichhammer, Peter
    Eriksson, Johan
    Escott-Price, Valentina
    Fanous, Ayman H.
    Farrell, Martilias S.
    Frank, Josef
    Franke, Lude
    Freedman, Robert
    Freimer, Nelson B.
    Friedl, Marion
    Friedman, Joseph, I
    Genovese, Giulio
    Georgieva, Lyudmila
    Giegling, Ina
    Giusti-Rodriguez, Paola
    Godard, Stephanie
    Goldstein, Jacqueline, I
    Golimbet, Vera
    Gopal, Srihari
    Gratten, Jacob
    de Haan, Lieuwe
    Hammer, Christian
    Hamshere, Marian L.
    Hansen, Mark
    Hansen, Thomas
    Hartmann, Annette M.
    Henskens, Frans A.
    Herms, Stefan
    Hirschhorn, Joel N.
    Hoffmann, Per
    Hofman, Andrea
    Hollegaard, Mads, V
    Ikeda, Masashi
    Joa, Inge
    Julia, Antonio
    Kahn, Rene S.
    Kalaydjieva, Luba
    Karachanak-Yankova, Sena
    Karjalainen, Juha
    Kavanagh, David
    Keller, Matthew C.
    Kennedy, James L.
    Khrunin, Andrey
    Kim, Yunjung
    Klovins, Janis
    Knowles, James A.
    Konte, Bettina
    Kucinskas, Vaidutis
    Kucinskiene, Zita Ausrele
    Kuzelova-Ptackova, Hana
    Kahler, Anna K.
    Laurent, Claudine
    Keong, Jimmy Lee Chee
    Lee, S. Hong
    Legge, Sophie E.
    Lerer, Bernard
    Li, Miaoxin
    Li, Tao
    Liang, Kung-Yee
    Lieberman, Jeffrey
    Limborska, Svetlana
    Loughland, Carmel M.
    Lubinski, Jan
    Lonnqvist, Jouko
    Macek, Milan, Jr.
    Magnusson, Patrik K. E.
    Maher, Brion S.
    Maier, Wolfgang
    Mallet, Jacques
    Marsal, Sara
    Mattingsdal, Morten
    McCarley, Robert W.
    McDonald, Colm
    McIntosh, Andrew M.
    Meier, Sandra
    Meijer, Carin J.
    Melegh, Bela
    Melle, Ingrid
    Mesholam-Gately, Raquelle, I
    Metspalu, Andres
    Michie, Patricia T.
    Milani, Lili
    Milanova, Vihra
    Mokrab, Younes
    Morris, Derek W.
    Murphy, Kieran C.
    Murray, Robin M.
    Myin-Germeys, Inez
    Muller-Myhsok, Bertram
    Nelis, Mari
    Nenadic, Igor
    Nertney, Deborah A.
    Nestadt, Gerald
    Nicodemus, Kristin K.
    Nikitina-Zake, Liene
    Nisenbaum, Laura
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    O'Callaghan, Eadbhard
    O'Dushlaine, Colm
    O'Neill, F. Anthony
    Oh, Sang-Yun
    Olincy, Ann
    Olsen, Line
    Van Os, Jim
    Pantelis, Christos
    Papadimitriou, George N.
    Papiol, Sergi
    Parkhomenko, Elena
    Pato, Michele T.
    Paunio, Tiina
    Pejovic-Milovancevic, Milica
    Perkins, Diana O.
    Pietilainen, Olli
    Pimm, Jonathan
    Pocklington, Andrew J.
    Powell, John
    Price, Alkes
    Pulver, Ann E.
    Purcell, Shaun M.
    Quested, Digby
    Rasmussen, Henrik B.
    Reichenberg, Abraham
    Reimers, Mark A.
    Richards, Alexander L.
    Roffman, Joshua L.
    Salomaa, Veikko
    Sanders, Alan R.
    Schall, Ulrich
    Schubert, Christian R.
    Schulze, Thomas G.
    Schwab, Sibylle G.
    Scolnick, Edward M.
    Scott, Rodney J.
    Seidman, Larry J.
    Shi, Jianxin
    Sigurdsson, Engilbert
    Silagadze, Teimuraz
    Silverman, Jeremy M.
    Sim, Kang
    Slominsky, Petr
    Smoller, Jordan W.
    So, Hon-Cheong
    Spencer, Chris C. A.
    Stefansson, Hreinn
    Steinberg, Stacy
    Stogmann, Elisabeth
    Straub, Richard E.
    Strengman, Eric
    Strohmaier, Jana
    Stroup, T. Scott
    Subramaniam, Mythily
    Suvisaari, Jaana
    Svrakic, Dragan M.
    Szatkiewicz, Jin P.
    Soderman, Erik
    Thirumalai, Srinivas
    Toncheva, Draga
    Tosato, Sarah
    Veijola, Juha
    Waddington, John
    Walsh, Dermot
    Wang, Dai
    Wang, Qiang
    Webb, Bradley T.
    Weiser, Mark
    Wildenauer, Dieter B.
    Williams, Nigel M.
    Williams, Stephanie
    Witt, Stephanie H.
    Wolen, Aaron R.
    Wong, Emily H. M.
    Wormley, Brandon K.
    Xi, Hualin Simon
    Zai, Clement C.
    Zheng, Xuebin
    Zimprich, Fritz
    Wray, Naomi R.
    Stefansson, Kari
    Visscher, Peter M.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Andreassen, Ole A.
    Blackwood, Douglas H. R.
    Bramon, Elvira
    Cichon, Sven
    Darvasi, Ariel
    Ehrenreich, Hannelore
    Esko, Tonu
    Gejman, Pablo, V
    Gill, Michael
    Gurling, Hugh
    Hultman, Christina M.
    Iwata, Nakao
    Jablensky, Assen, V
    Jonsson, Erik G.
    Kendler, Kenneth S.
    Kirov, George
    Knight, Jo
    Lencz, Todd
    Levinson, Douglas F.
    Li, Qingqin S.
    Liu, Jianjun
    Malhotra, Anil K.
    McCarroll, Steven A.
    McQuillin, Andrew
    Moran, Jennifer L.
    Mortensen, Preben B.
    Mowry, Bryan J.
    Nothen, Markus M.
    Ophoff, Roel A.
    Palotie, Aarno
    Pato, Carlos N.
    Petryshen, Tracey L.
    Posthuma, Danielle
    Rietschel, Marcella
    Riley, Brien P.
    Rujescu, Dan
    Sham, Pak C.
    St Clair, David
    Weinberger, Daniel R.
    Wendland, Jens R.
    Daly, Mark J.
    Sullivan, Patrick F.
    Gene expression imputation across multiple brain regions provides insights into schizophrenia risk2019Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 4, s. 659-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

  • 17. Huyghe, Jeroen R.
    et al.
    Bien, Stephanie A.
    Harrison, Tabitha A.
    Kang, Hyun Min
    Chen, Sai
    Schmit, Stephanie L.
    Conti, David V.
    Qu, Conghui
    Jeon, Jihyoun
    Edlund, Christopher K.
    Greenside, Peyton
    Wainberg, Michael
    Schumacher, Fredrick R.
    Smith, Joshua D.
    Levine, David M.
    Nelson, Sarah C.
    Sinnott-Armstrong, Nasa A.
    Albanes, Demetrius
    Alonso, M. Henar
    Anderson, Kristin
    Arnau-Collell, Coral
    Arndt, Volker
    Bamia, Christina
    Banbury, Barbara L.
    Baron, John A.
    Berndt, Sonja I.
    Bezieau, Stephane
    Bishop, D. Timothy
    Boehm, Juergen
    Boeing, Heiner
    Brenner, Hermann
    Brezina, Stefanie
    Buch, Stephan
    Buchanan, Daniel D.
    Burnett-Hartman, Andrea
    Butterbach, Katja
    Caan, Bette J.
    Campbell, Peter T.
    Carlson, Christopher S.
    Castellvi-Bel, Sergi
    Chan, Andrew T.
    Chang-Claude, Jenny
    Chanock, Stephen J.
    Chirlaque, Maria-Dolores
    Cho, Sang Hee
    Connolly, Charles M.
    Cross, Amanda J.
    Cuk, Katarina
    Curtis, Keith R.
    de la Chapelle, Albert
    Doheny, Kimberly F.
    Duggan, David
    Easton, Douglas F.
    Elias, Sjoerd G.
    Elliott, Faye
    English, Dallas R.
    Feskens, Edith J. M.
    Figueiredo, Jane C.
    Fischer, Rocky
    FitzGerald, Liesel M.
    Forman, David
    Gala, Manish
    Gallinger, Steven
    Gauderman, W. James
    Giles, Graham G.
    Gillanders, Elizabeth
    Gong, Jian
    Goodman, Phyllis J.
    Grady, William M.
    Grove, John S.
    Gsur, Andrea
    Gunter, Marc J.
    Haile, Robert W.
    Hampe, Jochen
    Hampel, Heather
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hayes, Richard B.
    Hofer, Philipp
    Hoffmeister, Michael
    Hopper, John L.
    Hsu, Wan-Ling
    Huang, Wen-Yi
    Hudson, Thomas J.
    Hunter, David J.
    Ibanez-Sanz, Gemma
    Idos, Gregory E.
    Ingersoll, Roxann
    Jackson, Rebecca D.
    Jacobs, Eric J.
    Jenkins, Mark A.
    Joshi, Amit D.
    Joshu, Corinne E.
    Keku, Temitope O.
    Key, Timothy J.
    Kim, Hyeong Rok
    Kobayashi, Emiko
    Kolonel, Laurence N.
    Kooperberg, Charles
    Kuehn, Tilman
    Kury, Sebastien
    Kweon, Sun-Seog
    Larsson, Susanna C.
    Laurie, Cecelia A.
    Le Marchand, Loic
    Leal, Suzanne M.
    Lee, Soo Chin
    Lejbkowicz, Flavio
    Lemire, Mathieu
    Li, Christopher I.
    Li, Li
    Lieb, Wolfgang
    Lin, Yi
    Lindblom, Annika
    Lindor, Noralane M.
    Ling, Hua
    Louie, Tin L.
    Mannisto, Satu
    Markowitz, Sanford D.
    Martin, Vicente
    Masala, Giovanna
    McNeil, Caroline E.
    Melas, Marilena
    Milne, Roger L.
    Moreno, Lorena
    Murphy, Neil
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Naccarati, Alessio
    Newcomb, Polly A.
    Offit, Kenneth
    Ogino, Shuji
    Onland-Moret, N. Charlotte
    Pardini, Barbara
    Parfrey, Patrick S.
    Pearlman, Rachel
    Perduca, Vittorio
    Pharoah, Paul D. P.
    Pinchev, Mila
    Platz, Elizabeth A.
    Prentice, Ross L.
    Pugh, Elizabeth
    Raskin, Leon
    Rennert, Gad
    Rennert, Hedy S.
    Riboli, Elio
    Rodriguez-Barranco, Miguel
    Romm, Jane
    Sakoda, Lori C.
    Schafmayer, Clemens
    Schoen, Robert E.
    Seminara, Daniela
    Shah, Mitul
    Shelford, Tameka
    Shin, Min-Ho
    Shulman, Katerina
    Sieri, Sabina
    Slattery, Martha L.
    Southey, Melissa C.
    Stadler, Zsofia K.
    Stegmaier, Christa
    Su, Yu-Ru
    Tangen, Catherine M.
    Thibodeau, Stephen N.
    Thomas, Duncan C.
    Thomas, Sushma S.
    Toland, Amanda E.
    Trichopoulou, Antonia
    Ulrich, Cornelia M.
    Van den Berg, David J.
    van Duijnhoven, Franzel J. B.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Kranen, Henk
    Vijai, Joseph
    Visvanathan, Kala
    Vodicka, Pavel
    Vodickova, Ludmila
    Vymetalkova, Veronika
    Weigl, Korbinian
    Weinstein, Stephanie J.
    White, Emily
    Win, Aung Ko
    Wolf, C. Roland
    Wolk, Alicja
    Woods, Michael O.
    Wu, Anna H.
    Zaidi, Syed H.
    Zanke, Brent W.
    Zhang, Qing
    Zheng, Wei
    Scacheri, Peter C.
    Potter, John D.
    Bassik, Michael C.
    Kundaje, Anshul
    Casey, Graham
    Moreno, Victor
    Abecasis, Goncalo R.
    Nickerson, Deborah A.
    Gruber, Stephen B.
    Hsu, Li
    Peters, Ulrike
    Discovery of common and rare genetic risk variants for colorectal cancer2019Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 1, s. 76-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

  • 18. Hüffmeier, Ulrike
    et al.
    Uebe, Steffen
    Ekici, Arif B
    Bowes, John
    Giardina, Emiliano
    Korendowych, Eleanor
    Juneblad, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Apel, Maria
    McManus, Ross
    Ho, Pauline
    Bruce, Ian N
    Ryan, Anthony W
    Behrens, Frank
    Lascorz, Jesús
    Böhm, Beate
    Traupe, Heiko
    Lohmann, Jörg
    Gieger, Christian
    Wichmann, Heinz-Erich
    Herold, Christine
    Steffens, Michael
    Klareskog, Lars
    Wienker, Thomas F
    Fitzgerald, Oliver
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    McHugh, Neil J
    Novelli, Giuseppe
    Burkhardt, Harald
    Barton, Anne
    Reis, André
    Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis2010Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, nr 11, s. 996-999Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10⁻¹⁷). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10⁻³). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10⁻²⁰, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

  • 19. Jacobs, Kevin B
    et al.
    Yeager, Meredith
    Zhou, Weiyin
    Wacholder, Sholom
    Wang, Zhaoming
    Rodriguez-Santiago, Benjamin
    Hutchinson, Amy
    Deng, Xiang
    Liu, Chenwei
    Horner, Marie-Josephe
    Cullen, Michael
    Epstein, Caroline G
    Burdett, Laurie
    Dean, Michael C
    Chatterjee, Nilanjan
    Sampson, Joshua
    Chung, Charles C
    Kovaks, Joseph
    Gapstur, Susan M
    Stevens, Victoria L
    Teras, Lauren T
    Gaudet, Mia M
    Albanes, Demetrius
    Weinstein, Stephanie J
    Virtamo, Jarmo
    Taylor, Philip R
    Freedman, Neal D
    Abnet, Christian C
    Goldstein, Alisa M
    Hu, Nan
    Yu, Kai
    Yuan, Jian-Min
    Liao, Linda
    Ding, Ti
    Qiao, You-Lin
    Gao, Yu-Tang
    Koh, Woon-Puay
    Xiang, Yong-Bing
    Tang, Ze-Zhong
    Fan, Jin-Hu
    Aldrich, Melinda C
    Amos, Christopher
    Blot, William J
    Bock, Cathryn H
    Gillanders, Elizabeth M
    Harris, Curtis C
    Haiman, Christopher A
    Henderson, Brian E
    Kolonel, Laurence N
    Le Marchand, Loic
    McNeill, Lorna H
    Rybicki, Benjamin A
    Schwartz, Ann G
    Signorello, Lisa B
    Spitz, Margaret R
    Wiencke, John K
    Wrensch, Margaret
    Wu, Xifeng
    Zanetti, Krista A
    Ziegler, Regina G
    Figueroa, Jonine D
    Garcia-Closas, Montserrat
    Malats, Nuria
    Marenne, Gaelle
    Prokunina-Olsson, Ludmila
    Baris, Dalsu
    Schwenn, Molly
    Johnson, Alison
    Landi, Maria Teresa
    Goldin, Lynn
    Consonni, Dario
    Bertazzi, Pier Alberto
    Rotunno, Melissa
    Rajaraman, Preetha
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Freeman, Laura E Beane
    Berg, Christine D
    Buring, Julie E
    Butler, Mary A
    Carreon, Tania
    Feychting, Maria
    Ahlbom, Anders
    Gaziano, J Michael
    Giles, Graham G
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hankinson, Susan E
    Hartge, Patricia
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Inskip, Peter D
    Johansen, Christoffer
    Landgren, Annelie
    McKean-Cowdin, Roberta
    Michaud, Dominique S
    Melin, Beatrice S
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Peters, Ulrike
    Ruder, Avima M
    Sesso, Howard D
    Severi, Gianluca
    Shu, Xiao-Ou
    Visvanathan, Kala
    White, Emily
    Wolk, Alicja
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Silverman, Debra T
    Kogevinas, Manolis
    Gonzalez, Juan R
    Villa, Olaya
    Li, Donghui
    Duell, Eric J
    Risch, Harvey A
    Olson, Sara H
    Kooperberg, Charles
    Wolpin, Brian M
    Jiao, Li
    Hassan, Manal
    Wheeler, William
    Arslan, Alan A
    Bueno-de-Mesquita, H Bas
    Fuchs, Charles S
    Gallinger, Steven
    Gross, Myron D
    Holly, Elizabeth A
    Klein, Alison P
    Lacroix, Andrea
    Mandelson, Margaret T
    Petersen, Gloria
    Boutron-Ruault, Marie-Christine
    Bracci, Paige M
    Canzian, Federico
    Chang, Kenneth
    Cotterchio, Michelle
    Giovannucci, Edward L
    Goggins, Michael
    Bolton, Judith A Hoffman
    Jenab, Mazda
    Khaw, Kay-Tee
    Krogh, Vittorio
    Kurtz, Robert C
    McWilliams, Robert R
    Mendelsohn, Julie B
    Rabe, Kari G
    Riboli, Elio
    Tjønneland, Anne
    Tobias, Geoffrey S
    Trichopoulos, Dimitrios
    Elena, Joanne W
    Yu, Herbert
    Amundadottir, Laufey
    Stolzenberg-Solomon, Rachael Z
    Kraft, Peter
    Schumacher, Fredrick
    Stram, Daniel
    Savage, Sharon A
    Mirabello, Lisa
    Andrulis, Irene L
    Wunder, Jay S
    García, Ana Patiño
    Sierrasesúmaga, Luis
    Barkauskas, Donald A
    Gorlick, Richard G
    Purdue, Mark
    Chow, Wong-Ho
    Moore, Lee E
    Schwartz, Kendra L
    Davis, Faith G
    Hsing, Ann W
    Berndt, Sonja I
    Black, Amanda
    Wentzensen, Nicolas
    Brinton, Louise A
    Lissowska, Jolanta
    Peplonska, Beata
    McGlynn, Katherine A
    Cook, Michael B
    Graubard, Barry I
    Kratz, Christian P
    Greene, Mark H
    Erickson, Ralph L
    Hunter, David J
    Thomas, Gilles
    Hoover, Robert N
    Real, Francisco X
    Fraumeni, Joseph F
    Caporaso, Neil E
    Tucker, Margaret
    Rothman, Nathaniel
    Pérez-Jurado, Luis A
    Chanock, Stephen J
    Detectable clonal mosaicism and its relationship to aging and cancer.2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 6, s. 651-658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

  • 20. Justice, Anne E.
    et al.
    Karaderi, Tugce
    Highland, Heather M.
    Young, Kristin L.
    Graff, Mariaelisa
    Lu, Yingchang
    Turcot, Valerie
    Auer, Paul L.
    Fine, Rebecca S.
    Guo, Xiuqing
    Schurmann, Claudia
    Lempradl, Adelheid
    Marouli, Eirini
    Mahajan, Anubha
    Winkler, Thomas W.
    Locke, Adam E.
    Medina-Gomez, Carolina
    Esko, Tonu
    Vedantam, Sailaja
    Giri, Ayush
    Lo, Ken Sin
    Alfred, Tamuno
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Heard-Costa, Nancy L.
    Feitosa, Mary F.
    Manning, Alisa K.
    Willems, Sara M.
    Sivapalaratnam, Suthesh
    Abecasis, Goncalo
    Alam, Dewan S.
    Allison, Matthew
    Amouyel, Philippe
    Arzumanyanm, Zorayr
    Balkau, Beverley
    Bastarache, Lisa
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Broer, Linda
    Burt, Amber A.
    Butterworth, Adam S.
    Caulfield, Markj
    Cesana, Giancarlo
    Chambers, John C.
    Chasman, Daniel, I
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audreyy
    Collins, Francis S.
    Cook, James P.
    Cox, Amanda J.
    Crosslin, David S.
    Danesh, John
    de Bakker, Paul I. W.
    de Denus, Simon
    de Mutsert, Renee
    Dedoussis, George
    Demerath, Ellen W.
    Dennis, Joe G.
    Denny, Josh C.
    Di Angelantonio, Emanuele
    Doerr, Marcus
    Drenos, Fotios
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Fornage, Myriam
    Fox, Caroline S.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Giedraitis, Vilmantas
    Girotto, Giorgia
    Gorski, Mathias
    Grallert, Harald
    Grarup, Niels
    Groves, Megan L.
    Gustafsson, Stefan
    Haessler, Jeff
    Hansen, Torben
    Hattersley, Andrew T.
    Hayward, Caroline
    Heid, Iris M.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Hung, Yi-Jen
    Hveem, Kristian
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jarvik, Gail P.
    Jia, Yucheng
    Jorgensen, Torben
    Jousilahti, Pekka
    Justesen, Johanne M.
    Kahali, Bratati
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kee, Frank
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kovacs, Peter
    Kraemer, Bernhard K.
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    La Nge, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lee, Wen-Jane
    Lehtimaeki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    RuifangLi-Gao,
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstroem, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    MacGregor, Stuart
    Magi, Reedik
    Mannisto, Satu
    Marenne, Gaelle
    Marten, Jonathan
    Mascal, Nicholas G. D.
    McCarthy, Mark, I
    Meidtner, Karina
    Mihailov, Evelin
    Moilanen, Leena
    Moitry, Marie
    Mook-Kanamori, Dennis O.
    Morgan, Anna
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Ntalla, Ioanna
    Owen, Katharine R.
    Pedersen, Oluf
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    James, A.
    Perry, John R. B.
    Pers, Tune H.
    Ewing, Ailith
    Polasek, Ozren
    Rasheed, Asif
    Raulerson, Chelsea K.
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Ridker, Paul M.
    Rivas, Manuel A.
    Robertson, Neil R.
    Robino, Antonietta
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Blair H.
    Smith, Jennifer A.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swart, Karin M. A.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Torres, Mina
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vanhala, Mauno
    Varma, Rohit
    Vermeulen, Sita H.
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wareham, N. Icholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Verges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zheng, He
    Zhou, Wei
    Zillikens, M. Carola
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Pospisilik, J. Andrew
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    Mohlke, Karen L.
    Rotter, Jerome, I
    Kutalik, Zoltan
    Hirschhorn, Joel N.
    Cupples, L. Adrienne
    Loos, Ruth J. F.
    North, Kari E.
    Lindgren, Cecilia M.
    O'Connell, Jeffrey R.
    Raitakari, Olli T.
    Lange, Leslie A.
    Uitterlinden, Andr G.
    Grove, Megan L.
    Masca, Nicholas G. D.
    Luan, Jianan
    Wareham, Nicholas J.
    Esko, Tnu
    De Bakker, Paul Iw
    Caulfield, Mark J.
    Mller-Nurasyid, Martina
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 3, s. 452-469Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 21. Kato, Norihiro
    et al.
    Loh, Marie
    Takeuchi, Fumihiko
    Verweij, Niek
    Wang, Xu
    Zhang, Weihua
    Kelly, Tanika N.
    Saleheen, Danish
    Lehne, Benjamin
    Leach, Irene Mateo
    Drong, Alexander W.
    Abbott, James
    Wahl, Simone
    Tan, Sian-Tsung
    Scott, William R.
    Campanella, Gianluca
    Chadeau-Hyam, Marc
    Afzal, Uzma
    Ahluwalia, Tarunveer S.
    Bonder, Marc Jan
    Chen, Peng
    Dehghan, Abbas
    Edwards, Todd L.
    Esko, Tonu
    Go, Min Jin
    Harris, Sarah E.
    Hartiala, Jaana
    Kasela, Silva
    Kasturiratne, Anuradhani
    Khor, Chiea-Chuen
    Kleber, Marcus E.
    Li, Huaixing
    Mok, Zuan Yu
    Nakatochi, Masahiro
    Sapari, Nur Sabrina
    Saxena, Richa
    Stewart, Alexandre F. R.
    Stolk, Lisette
    Tabara, Yasuharu
    Teh, Ai Ling
    Wu, Ying
    Wu, Jer-Yuarn
    Zhang, Yi
    Aits, Imke
    Alves, Alexessander Da Silva Couto
    Das, Shikta
    Dorajoo, Rajkumar
    Hopewell, Jemma C.
    Kim, Yun Kyoung
    Koivula, Robert W.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Nguyen, Quang N.
    Pereira, Mark A.
    Postmus, Iris
    Raitakari, Olli T.
    Bryan, Molly Scannell
    Scott, Robert A.
    Sorice, Rossella
    Tragante, Vinicius
    Traglia, Michela
    White, Jon
    Yamamoto, Ken
    Zhang, Yonghong
    Adair, Linda S.
    Ahmed, Alauddin
    Akiyama, Koichi
    Asif, Rasheed
    Aung, Tin
    Barroso, Ines
    Bjonnes, Andrew
    Braun, Timothy R.
    Cai, Hui
    Chang, Li-Ching
    Chen, Chien-Hsiun
    Cheng, Ching-Yu
    Chong, Yap-Seng
    Collins, Rory
    Courtney, Regina
    Davies, Gail
    Delgado, Graciela
    Do, Loi D.
    Doevendans, Pieter A.
    Gansevoort, Ron T.
    Gao, Yu-Tang
    Grammer, Tanja B.
    Grarup, Niels
    Grewal, Jagvir
    Gu, Dongfeng
    Wander, Gurpreet S.
    Hartikainen, Anna-Liisa
    Hazen, Stanley L.
    He, Jing
    Heng, Chew-Kiat
    Hixson, James E.
    Hofman, Albert
    Hsu, Chris
    Huang, Wei
    Husemoen, Lise L. N.
    Hwang, Joo-Yeon
    Ichihara, Sahoko
    Igase, Michiya
    Isono, Masato
    Justesen, Johanne M.
    Katsuy, Tomohiro
    Kibriya, Muhammad G.
    Kim, Young Jin
    Kishimoto, Miyako
    Koh, Woon-Puay
    Kohara, Katsuhiko
    Kumari, Meena
    Kwek, Kenneth
    Lee, Nanette R.
    Lee, Jeannette
    Liao, Jiemin
    Lieb, Wolfgang
    Liewald, David C. M.
    Matsubara, Tatsuaki
    Matsushita, Yumi
    Meitinger, Thomas
    Mihailov, Evelin
    Milani, Lili
    Mills, Rebecca
    Mononen, Nina
    Mueller-Nurasyid, Martina
    Nabika, Toru
    Nakashima, Eitaro
    Ng, Hong Kiat
    Nikus, Kjell
    Nutile, Teresa
    Ohkubo, Takayoshi
    Ohnaka, Keizo
    Parish, Sarah
    Paternoster, Lavinia
    Peng, Hao
    Peters, Annette
    Pham, Son T.
    Pinidiyapathirage, Mohitha J.
    Rahman, Mahfuzar
    Rakugi, Hiromi
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rozario, Michelle Ann
    Ruggiero, Daniela
    Sala, Cinzia F.
    Sarju, Ralhan
    Shimokawa, Kazuro
    Snieder, Harold
    Sparso, Thomas
    Spiering, Wilko
    Starr, John M.
    Stott, David J.
    Stram, Daniel O.
    Sugiyama, Takao
    Szymczak, Silke
    Tang, W. H. Wilson
    Tong, Lin
    Trompet, Stella
    Turjanmaa, Vaino
    Ueshima, Hirotsugu
    Uitterlinden, Andre G.
    Umemura, Satoshi
    Vaarasmaki, Marja
    van Dam, Rob M.
    van Gilst, Wiek H.
    van Veldhuisen, Dirk J.
    Viikari, Jorma S.
    Waldenberger, Melanie
    Wang, Yiqin
    Wang, Aili
    Wilson, Rory
    Wong, Tien-Yin
    Xiang, Yong-Bing
    Yamaguchi, Shuhei
    Ye, Xingwang
    Young, Robin D.
    Young, Terri L.
    Yuan, Jian-Min
    Zhou, Xueya
    Asselbergs, Folkert W.
    Ciullo, Marina
    Clarke, Robert
    Deloukas, Panos
    Franke, Andre
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Steve
    Friedlander, Yechiel
    Gross, Myron D.
    Guo, Zhirong
    Hansen, Torben
    Jarvelin, Marjo-Riitta
    Jorgensen, Torben
    Jukema, J. Wouter
    Kahonen, Mika
    Kajio, Hiroshi
    Kivimaki, Mika
    Lee, Jong-Young
    Lehtimaki, Terho
    Linneberg, Allan
    Miki, Tetsuro
    Pedersen, Oluf
    Samani, Nilesh J.
    Sorensen, Thorkild I. A.
    Takayanagi, Ryoichi
    Toniolo, Daniela
    Ahsan, Habibul
    Allayee, Hooman
    Chen, Yuan-Tsong
    Danesh, John
    Deary, Ian J.
    Franco, Oscar H.
    Franke, Lude
    Heijman, Bastiaan T.
    Holbrook, Joanna D.
    Isaacs, Aaron
    Kim, Bong-Jo
    Lin, Xu
    Liu, Jianjun
    Maerz, Winfried
    Metspalu, Andres
    Mohlke, Karen L.
    Sanghera, Dharambir K.
    Shu, Xiao-Ou
    van Meurs, Joyce B. J.
    Vithana, Eranga
    Wickremasinghe, Ananda R.
    Wijmenga, Cisca
    Wolffenbuttel, Bruce H. W.
    Yokota, Mitsuhiro
    Zheng, Wei
    Zhu, Dingliang
    Vineis, Paolo
    Kyrtopoulos, Soterios A.
    Kleinjans, Jos C. S.
    McCarthy, Mark I.
    Soong, Richie
    Gieger, Christian
    Scott, James
    Teo, Yik-Ying
    He, Jiang
    Elliott, Paul
    Tai, E. Shyong
    van der Harst, Pim
    Kooner, Jaspal S.
    Chambers, John C.
    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 11, s. 1282-1293Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

  • 22. Kenna, Kevin P.
    et al.
    van Doormaal, Perry T. C.
    Dekker, Annelot M.
    Ticozzi, Nicola
    Kenna, Brendan J.
    Diekstra, Frank P.
    van Rheenen, Wouter
    van Eijk, Kristel R.
    Jones, Ashley R.
    Keaglel, Pamela
    Shatunov, Aleksey
    Sproviero, William
    Smiths, Bradley N.
    van Es, Michael A.
    Topps, Simon D.
    Kenna, Aoife
    Miller, Jack W.
    Fallini, Claudia
    Tiloca, Cinzia
    McLaughlin, Russell L.
    Vance, Caroline
    Troakes, Claire
    Colombrita, Claudia
    Mora, Gabriele
    Calvo, Andrea
    Verde, Federico
    Al-Sarraj, Safa
    King, Andrew
    Calini, Daniela
    de Belleroche, Jacqueline
    Baas, Frank
    van der Kooi, Anneke J.
    de Visser, Marianne
    ten Asbroek, Anneloor L. M. A.
    Sapp, Peter C.
    McKenna-Yasek, Diane
    Polak, Meraida
    Asress, Seneshaw
    Luis Munoz-Blanco, Jose
    Strom, Tim M.
    Meitinger, Thomas
    Morrison, Karen E.
    Lauria, Giuseppe
    Williams, Kelly L.
    Leigh, P. Nigel
    Nicholson, Garth A.
    Blair, Ian P.
    Leblond, Claire S.
    Dion, Patrick A.
    Rouleau, Guy A.
    Pall, Hardev
    Shaw, Pamela J.
    Turner, Martin R.
    Talbot, Kevin
    Taroni, Franco
    Boylan, Kevin B.
    Van Blitterswijk, Marka
    Rademakers, Rosa
    Esteban-Perez, Jesus
    Garcia-Redondo, Alberto
    Van Damme, Phillip
    Robberecht, Wim
    Chio, Adrian
    Gellera, Cinzia
    Drepper, Carsten
    Sendtner, Michael
    Ratti, Antonia
    Glass, Jonathan D.
    Mora, Jesus S.
    Basak, Nazli A.
    Hardiman, Orla
    Ludolph, Albert C.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Weishaupt, Jochen H.
    Brown, Robert H., Jr.
    Al-Chalabi, Ammar
    Silani, Vincenzo
    Shaw, Christopher E.
    van den Berg, Leonard H.
    Veldink, Jan H.
    Landers, John E.
    D'Alfonso, Sandra
    Mazzini, Letizia
    Comi, Giacomo P.
    Del Bo, Roberto
    Ceroni, Mauro
    Gagliardi, Stella
    Querin, Giorgia
    Bertolin, Cinzia
    Pensato, Viviana
    Castellotti, Barbara
    Corti, Stefania
    Cereda, Cristina
    Corrado, Lucia
    Soraru, Gianni
    NEK1 variants confer susceptibility to amyotrophic lateral sclerosis2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 9, s. 1037-1042Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.

  • 23.
    Larsson, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Oyston, Petra C .F.
    Chain, Patrick
    Chu, May C.
    Duffield, Melanie
    Fuxelius, Hans-Erik
    Garcia, Emilio
    Hälltorp, Greger
    Johansson, Daniel
    Isherwood, Karen E.
    Karp, Peter D
    Larsson, Eva
    Liu, Ying
    Michell, Stephen
    Prior, Joann
    Prior, Richard
    Malfatti, Stephanie
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Svensson, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Thompson, Nick
    Vergez, Lisa
    Wagg, Jonathan K.
    Wren, Brendan W.
    Lindler, Luther E.
    Andersson, Siv G. E.
    Forsman, Mats
    FOI, Umeå, Sweden.
    Titball, Richard W.
    The complete genome sequence of Francisella tularensis, the causative agent of tularemia.2005Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 37, s. 153-159Artikkel i tidsskrift (Fagfellevurdert)
  • 24. Lenz, Tobias L.
    et al.
    Deutsch, Aaron J.
    Han, Buhm
    Hu, Xinli
    Okada, Yukinori
    Eyre, Stephen
    Knapp, Michael
    Zhernakova, Alexandra
    Huizinga, Tom W. J.
    Abecasis, Goncalo
    Becker, Jessica
    Boeckxstaens, Guy E.
    Chen, Wei-Min
    Franke, Andre
    Gladman, Dafna D.
    Gockel, Ines
    Gutierrez-Achury, Javier
    Martin, Javier
    Nair, Rajan P.
    Noethen, Markus M.
    Onengut-Gumuscu, Suna
    Rahman, Proton
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Stuart, Philip E.
    Tsoi, Lam C.
    van Heel, David A.
    Worthington, Jane
    Wouters, Mira M.
    Klareskog, Lars
    Elder, James T.
    Gregersen, Peter K.
    Schumacher, Johannes
    Rich, Stephen S.
    Wijmenga, Cisca
    Sunyaev, Shamil R.
    de Bakker, Paul I. W.
    Raychaudhuri, Soumya
    Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 9, s. 1085-1090Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.

  • 25. Lesseur, Corina
    et al.
    Diergaarde, Brenda
    Olshan, Andrew F
    Wünsch-Filho, Victor
    Ness, Andrew R
    Liu, Geoffrey
    Lacko, Martin
    Eluf-Neto, José
    Franceschi, Silvia
    Lagiou, Pagona
    Macfarlane, Gary J
    Richiardi, Lorenzo
    Boccia, Stefania
    Polesel, Jerry
    Kjaerheim, Kristina
    Zaridze, David
    Johansson, Mattias
    Menezes, Ana M
    Curado, Maria Paula
    Robinson, Max
    Ahrens, Wolfgang
    Canova, Cristina
    Znaor, Ariana
    Castellsagué, Xavier
    Conway, David I
    Holcátová, Ivana
    Mates, Dana
    Vilensky, Marta
    Healy, Claire M
    Szeszenia-Dąbrowska, Neonila
    Fabiánová, Eleonóra
    Lissowska, Jolanta
    Grandis, Jennifer R
    Weissler, Mark C
    Tajara, Eloiza H
    Nunes, Fabio D
    de Carvalho, Marcos B
    Thomas, Steve
    Hung, Rayjean J
    Peters, Wilbert H M
    Herrero, Rolando
    Cadoni, Gabriella
    Bueno-de-Mesquita, H Bas
    Steffen, Annika
    Agudo, Antonio
    Shangina, Oxana
    Xiao, Xiangjun
    Gaborieau, Valérie
    Chabrier, Amélie
    Anantharaman, Devasena
    Boffetta, Paolo
    Amos, Christopher I
    McKay, James D
    Brennan, Paul
    Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 12, s. 1544-1550Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

  • 26. Liu, Dajiang J.
    et al.
    Peloso, Gina M.
    Yu, Haojie
    Butterworth, Adam S.
    Wang, Xiao
    Mahajan, Anubha
    Saleheen, Danish
    Emdin, Connor
    Alam, Dewan
    Alves, Alexessander Couto
    Amouyel, Philippe
    Di Angelantonio, Emanuele
    Arveiler, Dominique
    Assimes, Themistocles L.
    Auer, Paul L.
    Baber, Usman
    Ballantyne, Christie M.
    Bang, Lia E.
    Benn, Marianne
    Bis, Joshua C.
    Boehnke, Michael
    Boerwinkle, Eric
    Bork-Jensen, Jette
    Bottinger, Erwin P.
    Brandslund, Ivan
    Brown, Morris
    Busonero, Fabio
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Chen, Y. Eugene
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audrey Y.
    Connell, John M.
    Cucca, Francesco
    Cupples, L. Adrienne
    Damrauer, Scott M.
    Davies, Gail
    Deary, Ian J.
    Dedoussis, George
    Denny, Joshua C.
    Dominiczak, Anna
    Dube, Marie-Pierre
    Ebeling, Tapani
    Eiriksdottir, Gudny
    Esko, Tonu
    Farmaki, Aliki-Eleni
    Feitosa, Mary F.
    Ferrario, Marco
    Ferrieres, Jean
    Ford, Ian
    Fornage, Myriam
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
    Frayling, Timothy M.
    Frikke-Schmidt, Ruth
    Fritsche, Lars G.
    Frossard, Philippe
    Fuster, Valentin
    Ganesh, Santhi K.
    Gao, Wei
    Garcia, Melissa E.
    Gieger, Christian
    Giulianini, Franco
    Goodarzi, Mark O.
    Grallert, Harald
    Grarup, Niels
    Groop, Leif
    Grove, Megan L.
    Gudnason, Vilmundur
    Hansen, Torben
    Harris, Tamara B.
    Hayward, Caroline
    Hirschhorn, Joel N.
    Holmen, Oddgeir L.
    Huffman, Jennifer
    Huo, Yong
    Hveem, Kristian
    Jabeen, Sehrish
    Jackson, Anne U.
    Jakobsdottir, Johanna
    Jarvelin, Marjo-Riitta
    Jensen, Gorm B.
    Jorgensen, Marit E.
    Jukema, J. Wouter
    Justesen, Johanne M.
    Kamstrup, Pia R.
    Kanoni, Stavroula
    Karpe, Fredrik
    Kee, Frank
    Khera, Amit V.
    Klarin, Derek
    Koistinen, Heikki A.
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo
    Langenberg, Claudia
    Langsted, Anne
    Launer, Lenore J.
    Lauritzen, Torsten
    Liewald, David C. M.
    Lin, Li An
    Linneberg, Allan
    Loos, Ruth J. F.
    Lu, Yingchang
    Lu, Xiangfeng
    Magi, Reedik
    Malarstig, Anders
    Manichaikul, Ani
    Manning, Alisa K.
    Mantyselka, Pekka
    Marouli, Eirini
    Masca, Nicholas G. D.
    Maschio, Andrea
    Meigs, James B.
    Melander, Olle
    Metspalu, Andres
    Morris, Andrew P.
    Morrison, Alanna C.
    Mulas, Antonella
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Neville, Matt J.
    Nielsen, Jonas B.
    Nielsen, Sune F.
    Nordestgaard, Borge G.
    Ordovas, Jose M.
    Mehran, Roxana
    O'Donnell, Christoper J.
    Orho-Melander, Marju
    Molony, Cliona M.
    Muntendam, Pieter
    Padmanabhan, Sandosh
    Palmer, Colin N. A.
    Pasko, Dorota
    Patel, Aniruddh P.
    Pedersen, Oluf
    Perola, Markus
    Peters, Annette
    Pisinger, Charlotta
    Pistis, Giorgio
    Polasek, Ozren
    Poulter, Neil
    Psaty, Bruce M.
    Rader, Daniel J.
    Rasheed, Asif
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rich, Stephen S.
    Ridker, Paul M.
    Rioux, John D.
    Robertson, Neil R.
    Roden, Dan M.
    Rotter, Jerome I.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Sanna, Serena
    Sattar, Naveed
    Schmidt, Ellen M.
    Scott, Robert A.
    Sever, Peter
    Sevilla, Raquel S.
    Shaffer, Christian M.
    Sim, Xueling
    Sivapalaratnam, Suthesh
    Small, Kerrin S.
    Smith, Albert V.
    Smith, Blair H.
    Somayajula, Sangeetha
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Starr, John M.
    Stirrups, Kathleen E.
    Stitziel, Nathan
    Strauch, Konstantin
    Stringham, Heather M.
    Surendran, Praveen
    Tada, Hayato
    Tall, Alan R.
    Tang, Hua
    Tardif, Jean-Claude
    Taylor, Kent D.
    Trompet, Stella
    Tsao, Philip S.
    Tuomilehto, Jaakko
    Tybjaerg-Hansen, Anne
    van Zuydam, Natalie R.
    Varbo, Anette
    Varga, Tibor V.
    Virtamo, Jarmo
    Waldenberger, Melanie
    Wang, Nan
    Wareham, Nick J.
    Warren, Helen R.
    Weeke, Peter E.
    Weinstock, Joshua
    Wessel, Jennifer
    Wilson, James G.
    Wilson, Peter W. F.
    Xu, Ming
    Yaghootkar, Hanieh
    Young, Robin
    Zeggini, Eleftheria
    Zhang, He
    Zheng, Neil S.
    Zhang, Weihua
    Zhang, Yan
    Zhou, Wei
    Zhou, Yanhua
    Zoledziewska, Magdalena
    Howson, Joanna M. M.
    Danesh, John
    McCarthy, Mark I.
    Cowan, Chad A.
    Abecasis, Goncalo
    Deloukas, Panos
    Musunuru, Kiran
    Willer, Cristen J.
    Kathiresan, Sekar
    Exome-wide association study of plasma lipids in > 300,000 individuals2017Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 12, s. 1758-1766Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

  • 27. Lo, Min-Tzu
    et al.
    Hinds, David A.
    Tung, Joyce Y.
    Franz, Carol
    Fan, Chun-Chieh
    Wang, Yunpeng
    Smeland, Olav B.
    Schork, Andrew
    Holland, Dominic
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Department of Radiology, University of California, San Diego, La Jolla, California, USA.
    Sanyal, Nilotpal
    Escott-Price, Valentina
    Smith, Daniel J.
    O'Donovan, Michael
    Stefansson, Hreinn
    Bjornsdottir, Gyda
    Thorgeirsson, Thorgeir E.
    Stefansson, Kari
    McEvoy, Linda K.
    Dale, Anders M.
    Andreassen, Ole A.
    Chen, Chi-Hua
    Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders2017Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 1, s. 152-156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Personality is influenced by genetic and environmental factors(1) and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci(2,3), significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132-260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422-18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit- hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion-introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety).

  • 28. Lotta, Luca A
    et al.
    Gulati, Pawan
    Day, Felix R
    Payne, Felicity
    Ongen, Halit
    van de Bunt, Martijn
    Gaulton, Kyle J
    Eicher, John D
    Sharp, Stephen J
    Luan, Jian'an
    De Lucia Rolfe, Emanuella
    Stewart, Isobel D
    Wheeler, Eleanor
    Willems, Sara M
    Adams, Claire
    Yaghootkar, Hanieh
    Forouhi, Nita G
    Khaw, Kay-Tee
    Johnson, Andrew D
    Semple, Robert K
    Frayling, Timothy
    Perry, John R B
    Dermitzakis, Emmanouil
    McCarthy, Mark I
    Barroso, Inês
    Wareham, Nicholas J
    Savage, David B
    Langenberg, Claudia
    O'Rahilly, Stephen
    Scott, Robert A
    Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

  • 29. Mahajan, Anubha
    et al.
    Wessel, Jennifer
    Willems, Sara M.
    Zhao, Wei
    Robertson, Neil R.
    Chu, Audrey Y.
    Gan, Wei
    Kitajima, Hidetoshi
    Taliun, Daniel
    Rayner, N. William
    Guo, Xiuqing
    Lu, Yingchang
    Li, Man
    Jensen, Richard A.
    Hu, Yao
    Huo, Shaofeng
    Lohman, Kurt K.
    Zhang, Weihua
    Cook, James P.
    Prins, Bram Peter
    Flannick, Jason
    Grarup, Niels
    Trubetskoy, Vassily Vladimirovich
    Kravic, Jasmina
    Kim, Young Jin
    Rybin, Denis V.
    Yaghootkar, Hanieh
    Mueller-Nurasyid, Martina
    Meidtner, Karina
    Li-Gao, Ruifang
    Varga, Tibor V.
    Marten, Jonathan
    Li, Jin
    Smith, Albert Vernon
    An, Ping
    Ligthart, Symen
    Gustafsson, Stefan
    Malerba, Giovanni
    Demirkan, Ayse
    Tajes, Juan Fernandez
    Steinthorsdottir, Valgerdur
    Wuttke, Matthias
    Lecoeur, Cecile
    Preuss, Michael
    Bielak, Lawrence F.
    Graff, Marielisa
    Highland, Heather M.
    Justice, Anne E.
    Liu, Dajiang J.
    Marouli, Eirini
    Peloso, Gina Marie
    Warren, Helen R.
    Afaq, Saima
    Afzal, Shoaib
    Ahlqvist, Emma
    Almgren, Peter
    Amin, Najaf
    Bang, Lia B.
    Bertoni, Alain G.
    Bombieri, Cristina
    Bork-Jensen, Jette
    Brandslund, Ivan
    Brody, Jennifer A.
    Burtt, Noel P.
    Canouil, Mickael
    Chen, Yii-Der Ida
    Cho, Yoon Shin
    Christensen, Cramer
    Eastwood, Sophie V.
    Eckardt, Kai-Uwe
    Fischer, Krista
    Gambaro, Giovanni
    Giedraitis, Vilmantas
    Grove, Megan L.
    de Haan, Hugoline G.
    Hackinger, Sophie
    Hai, Yang
    Han, Sohee
    Tybjaerg-Hansen, Anne
    Hivert, Marie-France
    Isomaa, Bo
    Jager, Susanne
    Jorgensen, Marit E.
    Jorgensen, Torben
    Karajamaki, Annemari
    Kim, Bong-Jo
    Kim, Sung Soo
    Koistinen, Heikki A.
    Kovacs, Peter
    Kriebel, Jennifer
    Kronenberg, Florian
    Lall, Kristi
    Lange, Leslie A.
    Lee, Jung-Jin
    Lehne, Benjamin
    Li, Huaixing
    Lin, Keng-Hung
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Jun
    Loh, Marie
    Magi, Reedik
    Mamakou, Vasiliki
    McKean-Cowdin, Roberta
    Nadkarni, Girish
    Neville, Matt
    Nielsen, Sune F.
    Ntalla, Ioanna
    Peyser, Patricia A.
    Rathmann, Wolfgang
    Rice, Kenneth
    Rich, Stephen S.
    Rode, Line
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Schonherr, Sebastian
    Selvin, Elizabeth
    Small, Kerrin S.
    Stancakova, Alena
    Surendran, Praveen
    Taylor, Kent D.
    Teslovich, Tanya M.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tin, Adrienne
    Tonjes, Anke
    Varbo, Anette
    Witte, Daniel R.
    Wood, Andrew R.
    Yajnik, Pranav
    Yao, Jie
    Yengo, Loic
    Young, Robin
    Amouyel, Philippe
    Boeing, Heiner
    Boerwinkle, Eric
    Bottinger, Erwin P.
    Chowdhury, Rajiv
    Collins, Francis S.
    Dedoussis, George
    Dehghan, Abbas
    Deloukas, Panos
    Ferrario, Marco M.
    Ferrieres, Jean
    Florez, Jose C.
    Frossard, Philippe
    Gudnason, Vilmundur
    Harris, Tamara B.
    Heckbert, Susan R.
    Howson, Joanna M. M.
    Ingelsson, Martin
    Kathiresan, Sekar
    Kee, Frank
    Kuusisto, Johanna
    Langenberg, Claudia
    Launer, Lenore J.
    Lindgren, Cecilia M.
    Mannisto, Satu
    Meitinger, Thomas
    Melander, Olle
    Mohlke, Karen L.
    Moitry, Marie
    Morris, Andrew D.
    Murray, Alison D.
    de Mutsert, Renee
    Orho-Melander, Marju
    Owen, Katharine R.
    Perola, Markus
    Peters, Annette
    Province, Michael A.
    Rasheed, Asif
    Ridker, Paul M.
    Rivadineira, Fernando
    Rosendaal, Frits R.
    Rosengren, Anders H.
    Salomaa, Veikko
    Sheu, Wayne H. -H.
    Sladek, Rob
    Smith, Blair H.
    Strauch, Konstantin
    Uitterlinden, Andre G.
    Varma, Rohit
    Willer, Cristen J.
    Bluher, Matthias
    Butterworth, Adam S.
    Chambers, John Campbell
    Chasman, Daniel I.
    Danesh, John
    van Duijn, Cornelia
    Dupuis, Josee
    Franco, Oscar H.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Froguel, Philippe
    Grallert, Harald
    Groop, Leif
    Han, Bok-Ghee
    Hansen, Torben
    Hattersley, Andrew T.
    Hayward, Caroline
    Ingelsson, Erik
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kooner, Jaspal Singh
    Kottgen, Anna
    Kuulasmaa, Kari
    Laakso, Markku
    Lin, Xu
    Lind, Lars
    Liu, Yongmei
    Loos, Ruth J. F.
    Marchini, Jonathan
    Metspalu, Andres
    Mook-Kanamori, Dennis
    Nordestgaard, Borge G.
    Palmer, Colin N. A.
    Pankow, James S.
    Pedersen, Oluf
    Psaty, Bruce M.
    Rauramaa, Rainer
    Sattar, Naveed
    Schulze, Matthias B.
    Soranzo, Nicole
    Spector, Timothy D.
    Stefansson, Kari
    Stumvoll, Michael
    Thorsteinsdottir, Unnur
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Wareham, Nicholas J.
    Wilson, James G.
    Zeggini, Eleftheria
    Scott, Robert A.
    Barroso, Ines
    Frayling, Timothy M.
    Goodarzi, Mark O.
    Meigs, James B.
    Boehnke, Michael
    Saleheen, Danish
    Morris, Andrew P.
    Rotter, Jerome I.
    McCarthy, Mark I.
    Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 559-571Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

  • 30. Manning, Alisa K.
    et al.
    Hivert, Marie-France
    Scott, Robert A.
    Grimsby, Jonna L.
    Bouatia-Naji, Nabila
    Chen, Han
    Rybin, Denis
    Liu, Ching-Ti
    Bielak, Lawrence F.
    Prokopenko, Inga
    Amin, Najaf
    Barnes, Daniel
    Cadby, Gemma
    Hottenga, Jouke-Jan
    Ingelsson, Erik
    Jackson, Anne U.
    Johnson, Toby
    Kanoni, Stavroula
    Ladenvall, Claes
    Lagou, Vasiliki
    Lahti, Jari
    Lecoeur, Cecile
    Liu, Yongmei
    Martinez-Larrad, Maria Teresa
    Montasser, May E.
    Navarro, Pau
    Perry, John R. B.
    Rasmussen-Torvik, Laura J.
    Salo, Perttu
    Sattar, Naveed
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Strawbridge, Rona J.
    Tanaka, Toshiko
    van Duijn, Cornelia M.
    An, Ping
    de Andrade, Mariza
    Andrews, Jeanette S.
    Aspelund, Thor
    Atalay, Mustafa
    Aulchenko, Yurii
    Balkau, Beverley
    Bandinelli, Stefania
    Beckmann, Jacques S.
    Beilby, John P.
    Bellis, Claire
    Bergman, Richard N.
    Blangero, John
    Boban, Mladen
    Boehnke, Michael
    Boerwinkle, Eric
    Bonnycastle, Lori L.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Boettcher, Yvonne
    Bouchard, Claude
    Brunner, Eric
    Budimir, Danijela
    Campbell, Harry
    Carlson, Olga
    Chines, Peter S.
    Clarke, Robert
    Collins, Francis S.
    Corbaton-Anchuelo, Arturo
    Couper, David
    de Faire, Ulf
    Dedoussis, George V.
    Deloukas, Panos
    Dimitriou, Maria
    Egan, Josephine M.
    Eiriksdottir, Gudny
    Erdos, Michael R.
    Eriksson, Johan G.
    Eury, Elodie
    Ferrucci, Luigi
    Ford, Ian
    Forouhi, Nita G.
    Fox, Caroline S.
    Franzosi, Maria Grazia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Frayling, Timothy M.
    Froguel, Philippe
    Galan, Pilar
    de Geus, Eco
    Gigante, Bruna
    Glazer, Nicole L.
    Goel, Anuj
    Groop, Leif
    Gudnason, Vilmundur
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hamsten, Anders
    Hansson, Ola
    Harris, Tamara B.
    Hayward, Caroline
    Heath, Simon
    Hercberg, Serge
    Hicks, Andrew A.
    Hingorani, Aroon
    Hofman, Albert
    Hui, Jennie
    Hung, Joseph
    Jarvelin, Marjo-Riitta
    Jhun, Min A.
    Johnson, Paul C. D.
    Jukema, J. Wouter
    Jula, Antti
    Kao, W. H.
    Kaprio, Jaakko
    Kardia, Sharon L. R.
    Keinanen-Kiukaanniemi, Sirkka
    Kivimaki, Mika
    Kolcic, Ivana
    Kovacs, Peter
    Kumari, Meena
    Kuusisto, Johanna
    Kyvik, Kirsten Ohm
    Laakso, Markku
    Lakka, Timo
    Lannfelt, Lars
    Lathrop, G. Mark
    Launer, Lenore J.
    Leander, Karin
    Li, Guo
    Lind, Lars
    Lindstrom, Jaana
    Lobbens, Stephane
    Loos, Ruth J. F.
    Luan, Jian'an
    Lyssenko, Valeriya
    Magi, Reedik
    Magnusson, Patrik K. E.
    Marmot, Michael
    Meneton, Pierre
    Mohlke, Karen L.
    Mooser, Vincent
    Morken, Mario A.
    Miljkovic, Iva
    Narisu, Narisu
    O'Connell, Jeff
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Lyle J.
    Palotie, Aarno
    Pankow, James S.
    Peden, John F.
    Pedersen, Nancy L.
    Pehlic, Marina
    Peltonen, Leena
    Penninx, Brenda
    Pericic, Marijana
    Perola, Markus
    Perusse, Louis
    Peyser, Patricia A.
    Polasek, Ozren
    Pramstaller, Peter P.
    Province, Michael A.
    Raikkonen, Katri
    Rauramaa, Rainer
    Rehnberg, Emil
    Rice, Ken
    Rotter, Jerome I.
    Rudan, Igor
    Ruokonen, Aimo
    Saaristo, Timo
    Sabater-Lleal, Maria
    Salomaa, Veikko
    Savage, David B.
    Saxena, Richa
    Schwarz, Peter
    Seedorf, Udo
    Sennblad, Bengt
    Serrano-Rios, Manuel
    Shuldiner, Alan R.
    Sijbrands, Eric J. G.
    Siscovick, David S.
    Smit, Johannes H.
    Small, Kerrin S.
    Smith, Nicholas L.
    Smith, Albert Vernon
    Stancakova, Alena
    Stirrups, Kathleen
    Stumvoll, Michael
    Sun, Yan V.
    Swift, Amy J.
    Toenjes, Anke
    Tuomilehto, Jaakko
    Trompet, Stella
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Vikstrom, Max
    Vitart, Veronique
    Vohl, Marie-Claude
    Voight, Benjamin F.
    Vollenweider, Peter
    Waeber, Gerard
    Waterworth, Dawn M.
    Watkins, Hugh
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wheeler, Eleanor
    Widen, Elisabeth
    Wild, Sarah H.
    Willems, Sara M.
    Willemsen, Gonneke
    Wilson, James F.
    Witteman, Jacqueline C. M.
    Wright, Alan F.
    Yaghootkar, Hanieh
    Zelenika, Diana
    Zemunik, Tatijana
    Zgaga, Lina
    Wareham, Nicholas J.
    McCarthy, Mark I.
    Barroso, Ines
    Watanabe, Richard M.
    Florez, Jose C.
    Dupuis, Josee
    Meigs, James B.
    Langenberg, Claudia
    A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 6, s. 659-669Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

  • 31. Marshall, Christian R.
    et al.
    Howrigan, Daniel P.
    Merico, Daniele
    Thiruvahindrapuram, Bhooma
    Wu, Wenting
    Greer, Douglas S.
    Antaki, Danny
    Shetty, Aniket
    Holmans, Peter A.
    Pinto, Dalila
    Gujral, Madhusudan
    Brandler, William M.
    Malhotra, Dheeraj
    Wang, Zhouzhi
    Fajarado, Karin V. Fuentes
    Maile, Michelle S.
    Ripke, Stephan
    Agartz, Ingrid
    Albus, Margot
    Alexander, Madeline
    Amin, Farooq
    Atkins, Joshua
    Bacanu, Silviu A.
    Belliveau, Richard A., Jr.
    Bergen, Sarah E.
    Ertalan, Marcelo
    Bevilacqua, Elizabeth
    Bigdeli, Tim B.
    Black, Donald W.
    Bruggeman, Richard
    Buccola, Nancy G.
    Buckner, Randy L.
    Bulik-Sullivan, Brendan
    Byerley, William
    Cahn, Wiepke
    Cai, Guiqing
    Cairns, Murray J.
    Campion, Dominique
    Cantor, Rita M.
    Carr, Vaughan J.
    Carrera, Noa
    Catts, Stanley V.
    Chambert, Kimberley D.
    Cheng, Wei
    Cloninger, C. Robert
    Cohen, David
    Cormican, Paul
    Craddock, Nick
    Crespo-Facorro, Benedicto
    Crowley, James J.
    Curtis, David
    Davidson, Michael
    Davis, Kenneth L.
    Degenhardt, Franziska
    Del Favero, Jurgen
    DeLisi, Lynn E.
    Dikeos, Dimitris
    Dinan, Timothy
    Djurovic, Srdjan
    Donohoe, Gary
    Drapeau, Elodie
    Duan, Jubao
    Dudbridge, Frank
    Eichhammer, Peter
    Eriksson, Johan
    Escott-Price, Valentina
    Essioux, Laurent
    Fanous, Ayman H.
    Farh, Kai-How
    Farrell, Martilias S.
    Frank, Josef
    Franke, Lude
    Freedman, Robert
    Freimer, Nelson B.
    Friedman, Joseph I.
    Forstner, Andreas J.
    Fromer, Menachem
    Genovese, Giulio
    Georgieva, Lyudmila
    Gershon, Elliot S.
    Giegling, Ina
    Giusti-Rodriguez, Paola
    Godard, Stephanie
    Goldstein, Jacqueline I.
    Gratten, Jacob
    de Haan, Lieuwe
    Hamshere, Marian L.
    Hansen, Mark
    Hansen, Thomas
    Haroutunian, Vahram
    Hartmann, Annette M.
    Henskens, Frans A.
    Herms, Stefan
    Hirschhorn, Joel N.
    Hoffinann, Per
    Hofman, Andrea
    Huang, Hailiang
    Ikeda, Masashi
    Joa, Inge
    Kahler, Anna K.
    Kahn, Rene S.
    Kalaydjieva, Luba
    Karjalainen, Juha
    Kavanagh, David
    Keller, Matthew C.
    Kelly, Brian J.
    Kennedy, James L.
    Kim, Yunjung
    Knowles, James A.
    Konte, Bettina
    Laurent, Claudine
    Lee, Phil
    Lee, S. Hong
    Legge, Sophie E.
    Lerer, Bernard
    Levy, Deborah L.
    Liang, Kung-Yee
    Lieberman, Jeffrey
    Lonnqvist, Jouko
    Loughland, Carmel M.
    Magnusson, Patrik K. E.
    Maher, Brion S.
    Maier, Wolfgang
    Mallet, Jacques
    Mattheisen, Manuel
    Mattingsdal, Morten
    McCarley, Robert W.
    McDonald, Colm
    McIntosh, Andrew M.
    Meier, Sandra
    Meijer, Carin J.
    Melle, Ingrid
    Mesholam-Gately, Raquelle I.
    Metspalu, Andres
    Michie, Patricia T.
    Milani, Lili
    Milanova, Vihra
    Mokrab, Younes
    Morris, Derek W.
    Muller-Myhsok, Bertram
    Murphy, Kieran C.
    Murray, Robin M.
    Myin-Germeys, Inez
    Nenadic, Igor
    Nertney, Deborah A.
    Nestadt, Gerald
    Nicodemus, Kristin K.
    Nisenbaum, Laura
    Nordin, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    O'Callaghan, Eadbhard
    O'Dushlaine, Colm
    Oh, Sang-Yun
    Olincy, Ann
    Olsen, Line
    O'Neill, F. Anthony
    Van Os, Jim
    Pantelis, Christos
    Papadimitriou, George N.
    Parkhomenko, Elena
    Pato, Michele T.
    Paunio, Tiina
    Perkins, Diana O.
    Pers, Tune H.
    Pietilainen, Olli
    Pimm, Jonathan
    Pocklington, Andrew J.
    Powell, John
    Price, Alkes
    Pulver, Ann E.
    Purcell, Shaun M.
    Quested, Digby
    Rasmussen, Henrik B.
    Reichenberg, Abraham
    Reimers, Mark A.
    Richards, Alexander L.
    Roffman, Joshua L.
    Roussos, Panos
    Ruderfer, Douglas M.
    Salomaa, Veikko
    Sanders, Alan R.
    Savitz, Adam
    Schall, Ulrich
    Schulze, Thomas G.
    Schwab, Sibylle G.
    Scolnick, Edward M.
    Scott, Rodney J.
    Seidman, Larry J.
    Shi, Jianxin
    Silverman, Jeremy M.
    Smoller, Jordan W.
    Soderman, Erik
    Spencer, Chris C. A.
    Stahl, Eli A.
    Strengman, Eric
    Strohmaier, Jana
    Stroup, T. Scott
    Suvisaari, Jaana
    Svrakic, Dragan M.
    Szatkiewicz, Jin P.
    Thirumalai, Srinivas
    Tooney, Paul A.
    Veijola, Juha
    Visscher, Peter M.
    Waddington, John
    Walsh, Dermot
    Webb, Bradley T.
    Weiser, Mark
    Wildenauer, Dieter B.
    Williams, Nigel M.
    Williams, Stephanie
    Witt, Stephanie H.
    Wolen, Aaron R.
    Wormley, Brandon K.
    Wray, Naomi R.
    Wu, Jing Qin
    Zai, Clement C.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Andreassen, Ole A.
    Blackwood, Douglas H. R.
    Bramon, Elvira
    Buxbaum, Joseph D.
    Cichon, Sven
    Collier, David A.
    Corvin, Aiden
    Daly, Mark J.
    Darvasi, Ariel
    Domenici, Enrico
    Esko, Tonu
    Gejman, Pablo V.
    Gill, Michael
    Gurling, Hugh
    Hultman, Christina M.
    Iwata, Nakao
    Jablensky, Assen V.
    Jonsson, Erik G.
    Kendler, Kenneth S.
    Kirov, George
    Knight, Jo
    Levinson, Douglas F.
    Li, Qingqin S.
    McCarroll, Steven A.
    McQuillin, Andrew
    Moran, Jennifer L.
    Mowry, Bryan J.
    Nothen, Markus M.
    Ophoff, Roel A.
    Owen, Michael J.
    Palotie, Aarno
    Pato, Carlos N.
    Petryshen, Tracey L.
    Posthuma, Danielle
    Rietschel, Marcella
    Riley, Brien P.
    Rujescu, Dan
    Sklar, Pamela
    St Clair, David
    Walters, James T. R.
    Werge, Thomas
    Siillivan, Patrick F.
    O'Donovan, Michael C.
    Scherer, Stephen W.
    Neale, Benjamin M.
    Sebat, Jonathan
    Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects2017Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 1, s. 27-35Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

  • 32. McKay, James D.
    et al.
    Hung, Rayjean J.
    Han, Younghun
    Zong, Xuchen
    Carreras-Torres, Robert
    Christiani, David C.
    Caporaso, Neil E.
    Johansson, Mattias
    Xiao, Xiangjun
    Li, Yafang
    Byun, Jinyoung
    Dunning, Alison
    Pooley, Karen A.
    Qian, David C.
    Ji, Xuemei
    Liu, Geoffrey
    Timofeeva, Maria N.
    Bojesen, Stig E.
    Wu, Xifeng
    Le Marchand, Loic
    Albanes, Demetrios
    Bickeböller, Heike
    Aldrich, Melinda C.
    Bush, William S.
    Tardon, Adonina
    Rennert, Gad
    Teare, M. Dawn
    Field, John K.
    Kiemeney, Lambertus A.
    Lazarus, Philip
    Haugen, Aage
    Lam, Stephen
    Schabath, Matthew B.
    Andrew, Angeline S.
    Shen, Hongbing
    Hong, Yun-Chul
    Yuan, Jian-Min
    Bertazzi, Pier Alberto
    Pesatori, Angela C.
    Ye, Yuanqing
    Diao, Nancy
    Su, Li
    Zhang, Ruyang
    Brhane, Yonathan
    Leighl, Natasha
    Johansen, Jakob S.
    Mellemgaard, Anders
    Saliba, Walid
    Haiman, Christopher A.
    Wilkens, Lynne R.
    Fernandez-Somoano, Ana
    Fernandez-Tardon, Guillermo
    van der Heijden, Henricus F. M.
    Kim, Jin Hee
    Dai, Juncheng
    Hu, Zhibin
    Davies, Michael P. A.
    Marcus, Michael W.
    Brunnström, Hans
    Manjer, Jonas
    Melander, Olle
    Muller, David C.
    Overvad, Kim
    Trichopoulou, Antonia
    Tumino, Rosario
    Doherty, Jennifer A.
    Barnett, Matt P.
    Chen, Chu
    Goodman, Gary E.
    Cox, Angela
    Taylor, Fiona
    Woll, Penella
    Brüske, Irene
    Wichmann, H-Erich
    Manz, Judith
    Muley, Thomas R.
    Risch, Angela
    Rosenberger, Albert
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Shepherd, Frances A.
    Tsao, Ming-Sound
    Arnold, Susanne M.
    Haura, Eric B.
    Bolca, Ciprian
    Holcatova, Ivana
    Janout, Vladimir
    Kontic, Milica
    Lissowska, Jolanta
    Mukeria, Anush
    Ognjanovic, Simona
    Orlowski, Tadeusz M.
    Scelo, Ghislaine
    Swiatkowska, Beata
    Zaridze, David
    Bakke, Per
    Skaug, Vidar
    Zienolddiny, Shanbeh
    Duell, Eric J.
    Butler, Lesley M.
    Koh, Woon-Puay
    Gao, Yu-Tang
    Houlston, Richard S.
    McLaughlin, John
    Stevens, Victoria L.
    Joubert, Philippe
    Lamontagne, Maxime
    Nickle, David C.
    Obeidat, Ma'en
    Timens, Wim
    Zhu, Bin
    Song, Lei
    Kachuri, Linda
    Artigas, Maria Soler
    Tobin, Martin D.
    Wain, Louise V.
    Rafnar, Thorunn
    Thorgeirsson, Thorgeir E.
    Reginsson, Gunnar W.
    Stefansson, Kari
    Hancock, Dana B.
    Bierut, Laura J.
    Spitz, Margaret R.
    Gaddis, Nathan C.
    Lutz, Sharon M.
    Gu, Fangyi
    Johnson, Eric O.
    Kamal, Ahsan
    Pikielny, Claudio
    Zhu, Dakai
    Lindström, Sara
    Jiang, Xia
    Tyndale, Rachel F.
    Chenevix-Trench, Georgia
    Beesley, Jonathan
    Bossé, Yohan
    Chanock, Stephen
    Brennan, Paul
    Landi, Maria Teresa
    Amos, Christopher I.
    Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes2017Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 7, s. 1126-1132Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.