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  • 1. Ahmad, S.
    et al.
    Zhao, W.
    Renström, F.
    Rasheed, A.
    Zaidi, M.
    Samuel, M.
    Shah, N.
    Mallick, N. H.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Zaman, K. S.
    Ishaq, M.
    Rasheed, S. Z.
    Memon, F-ur-R
    Hanif, B.
    Lakhani, M. S.
    Ahmed, F.
    Kazmi, S. U.
    Deloukas, P.
    Frossard, P.
    Franks, P. W.
    Saleheen, D.
    A novel interaction between theFLJ33534locus and smokingin obesity: a genome-wide study of 14 131 Pakistani adults2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 1, 186-190 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene-lifestyle interactions in obesity. METHODS: In the Pakistan Risk of Myocardial Infraction Study, a cross-sectional study based in Pakistan, we calculated body mass index (BMI) variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age(2), sex and genetic ancestry. RESULTS: The GWHVA analyses identified an intronic variant, rs140133294, in the FLJ33544 gene in association with BMI variance (P-value = 3.1 x 10(-8)). In explicit tests of gene x lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction = 0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never smokers. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction. CONCLUSIONS: In summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.

  • 2. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Lund University.
    Ericson, Ulrika
    Koivula, Robert W
    Chu, Audrey Y
    Rose, Lynda M
    Ganna, Andrea
    Qi, Qibin
    Stancakova, Alena
    Sandholt, Camilla H
    Elks, Cathy E
    Curhan, Gary
    Jensen, Majken K
    Tamimi, Rulla M
    Allin, Kristine H
    Jorgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Pare, Guillaume
    Magnusson, Patrik KE
    Pedersen, Nancy L
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L
    Pasquale, Louis T
    Pedersen, Oluf
    Scott, Robert A
    Ridker, Paul M
    Ingelsson, Erik
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J
    Chasman, Daniel I
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hu, Frank B
    Renström, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Lund University and Harvard University.
    Gene x physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 7, e1003607- p.Article in journal (Refereed)
    Abstract [en]

    Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

  • 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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 architecture2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 5, 501-U69 p.Article in journal (Refereed)
    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. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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 University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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 disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 1, 25-U52 p.Article in journal (Refereed)
    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.

  • 5. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. 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 disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, 1345-+ p.Article in journal (Refereed)
    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.

  • 6. Kanoni, Stavroula
    et al.
    Nettleton, Jennifer A
    Hivert, Marie-France
    Ye, Zheng
    van Rooij, Frank JA
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Sonestedt, Emily
    Ngwa, Julius S
    Wojczynski, Mary K
    Lemaitre, Rozenn N
    Gustafsson, Stefan
    Anderson, Jennifer S
    Tanaka, Toshiko
    Hindy, George
    Saylor, Georgia
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Bennett, Amanda J
    van Duijn, Cornelia M
    Florez, Jose C
    Fox, Caroline S
    Hofman, Albert
    Hoogeveen, Ron C
    Houston, Denise K
    Hu, Frank B
    Jacques, Paul F
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lind, Lars
    Liu, Yongmei
    McKeown, Nicola
    Ordovas, Jose
    Pankow, James S
    Sijbrands, Eric JG
    Syvänen, Ann-Christine
    Uitterlinden, André G
    Yannakoulia, Mary
    Zillikens, M Carola
    Wareham, Nick J
    Prokopenko, Inga
    Bandinelli, Stefania
    Forouhi, Nita G
    Cupples, L Adrienne
    Loos, Ruth J
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dupuis, Josée
    Langenberg, Claudia
    Ferrucci, Luigi
    Kritchevsky, Stephen B
    McCarthy, Mark I
    Ingelsson, Erik
    Borecki, Ingrid B
    Witteman, Jacqueline CM
    Orho-Melander, Marju
    Siscovick, David S
    Meigs, James B
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Dedoussis, George V
    Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis2011In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 9, 2407-2416 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants.

    RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes.

    RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: -0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant.

    CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

  • 7. Kilpeläinen, Tuomas O
    et al.
    Qi, Lu
    Brage, Soren
    Sharp, Stephen J
    Sonestedt, Emily
    Demerath, Ellen
    Ahmad, Tariq
    Mora, Samia
    Kaakinen, Marika
    Sandholt, Camilla Helene
    Holzapfel, Christina
    Autenrieth, Christine S
    Hyppönen, Elina
    Cauchi, Stéphane
    He, Meian
    Kutalik, Zoltan
    Kumari, Meena
    Stančáková, Alena
    Meidtner, Karina
    Balkau, Beverley
    Tan, Jonathan T
    Mangino, Massimo
    Timpson, Nicholas J
    Song, Yiqing
    Zillikens, M Carola
    Jablonski, Kathleen A
    Garcia, Melissa E
    Johansson, Stefan
    Bragg-Gresham, Jennifer L
    Wu, Ying
    van Vliet-Ostaptchouk, Jana V
    Onland-Moret, N Charlotte
    Zimmermann, Esther
    Rivera, Natalia V
    Tanaka, Toshiko
    Stringham, Heather M
    Silbernagel, Günther
    Kanoni, Stavroula
    Feitosa, Mary F
    Snitker, Soren
    Ruiz, Jonatan R
    Metter, Jeffery
    Larrad, Maria Teresa Martinez
    Atalay, Mustafa
    Hakanen, Maarit
    Amin, Najaf
    Cavalcanti-Proença, Christine
    Grøntved, Anders
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, John-Olov
    Kuusisto, Johanna
    Kähönen, Mika
    Lutsey, Pamela L
    Nolan, John J
    Palla, Luigi
    Pedersen, Oluf
    Pérusse, Louis
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Scott, Robert A
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sovio, Ulla
    Tammelin, Tuija H
    Rönnemaa, Tapani
    Lakka, Timo A
    Uusitupa, Matti
    Rios, Manuel Serrano
    Ferrucci, Luigi
    Bouchard, Claude
    Meirhaeghe, Aline
    Fu, Mao
    Walker, Mark
    Borecki, Ingrid B
    Dedoussis, George V
    Fritsche, Andreas
    Ohlsson, Claes
    Boehnke, Michael
    Bandinelli, Stefania
    van Duijn, Cornelia M
    Ebrahim, Shah
    Lawlor, Debbie A
    Gudnason, Vilmundur
    Harris, Tamara B
    Sørensen, Thorkild I A
    Mohlke, Karen L
    Hofman, Albert
    Uitterlinden, André G
    Tuomilehto, Jaakko
    Lehtimäki, Terho
    Raitakari, Olli
    Isomaa, Bo
    Njølstad, Pål R
    Florez, Jose C
    Liu, Simin
    Ness, Andy
    Spector, Timothy D
    Tai, E Shyong
    Froguel, Philippe
    Boeing, Heiner
    Laakso, Markku
    Marmot, Michael
    Bergmann, Sven
    Power, Chris
    Khaw, Kay-Tee
    Chasman, Daniel
    Ridker, Paul
    Hansen, Torben
    Monda, Keri L
    Illig, Thomas
    Järvelin, Marjo-Riitta
    Wareham, Nicholas J
    Hu, Frank B
    Groop, Leif C
    Orho-Melander, Marju
    Ekelund, Ulf
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Loos, Ruth J F
    Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children2011In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 8, no 11, e1001116- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).

    METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.

    CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

  • 8. Locke, Adam E.
    et al.
    Kahali, Bratati
    Berndt, Sonja I.
    Justice, Anne E.
    Pers, Tune H.
    Day, Felix R.
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L.
    Yang, Jian
    Croteau-Chonka, Damien C.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gustafsson, Stefan
    Kutalik, Zoltan
    Luan, Jian'an
    Maegi, Reedik
    Randall, Joshua C.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Faul, Jessica D.
    Smith, Jennifer A.
    Zhao, Jing Hua
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Asa K.
    Karjalainen, Juha
    Schmidt, Ellen M.
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L.
    Bragg-Gresham, L.
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B.
    Feenstra, Bjarke
    Feitosa, Mary F.
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U.
    Kanoni, Stavroula
    Kleber, Marcus E.
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Leach, Irene Mateo
    Medina-Gomez, Carolina
    Medland, Sarah E.
    Nalls, Michael A.
    Palmer, Cameron D.
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J.
    Prokopenko, Inga
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Stancakova, Alena
    Strawbridge, Rona J.
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W.
    van Settee, Jessica
    Van Vliet-Ostaptchouk, Jana V.
    Wang, Zhaoming
    Yengo, Loic
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Arnlov, Johan
    Arscott, Gillian M.
    Attwood, Antony P.
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N.
    Bellis, Claire
    Bennett, Amanda J.
    Berne, Christian
    Blagieva, Roza
    Blueher, Matthias
    Bohringer, Stefan
    Bonnycastle, Lori L.
    Boettcher, Yvonne
    Boyd, Heather A.
    Bruinenberg, Marcel
    Caspersen, Ida H.
    Chen, Yii-Der Ida
    Clarke, Robert
    Daw, E. Warwick
    de Craen, Anton J. M.
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S. F.
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M.
    Garcia, Melissa E.
    Geller, Frank
    Giedraitis, Vilmantas
    Gigante, Bruna
    Go, Alan S.
    Golay, Alain
    Goodall, Alison H.
    Gordon, Scott D.
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grallert, Harald
    Grammer, Tanja B.
    Graessler, Jurgen
    Gronberg, Henrik
    Groves, Christopher J.
    Gusto, Gaeelle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hartman, Catharina A.
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Helmer, Qinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L.
    Jeff, Janina M.
    Johansson, Asa
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R.
    Lichtner, Peter
    Lind, Lars
    Lindstrom, Jaana
    Lo, Ken Sin
    Lobbens, Stephane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, Francois
    Magnusson, Patrik K. E.
    Mahajan, Anubha
    McArdle, Wendy L.
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L.
    Morken, Mario A.
    Mulas, Antonella
    Mueller, Gabriele
    Mueller-Nurasyid, Martina
    Musk, Arthur W.
    Nagaraja, Ramaiah
    Noethen, Markus M.
    Nolte, Ilja M.
    Pilz, Stefan
    Rayner, Nigel W.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Rettig, Rainer
    Ried, Janina S.
    Ripke, Stephan
    Robertson, Neil R.
    Rose, Lynda M.
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R.
    Scott, William R.
    Seufferlein, Thomas
    Shi, Jianxin
    Smith, Albert Vernon
    Smolonska, Joanna
    Stanton, Alice V.
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M.
    Sundstrom, Johan
    Swertz, Morris A.
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tan, Sian-Tsung
    Tayo, Bamidele O.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P.
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C.
    Vermeulen, Sita H.
    Verweij, Niek
    Vonk, Judith M.
    Waite, Lindsay L.
    Warren, Helen R.
    Waterworth, Dawn
    Weedon, Michael N.
    Wilkens, Lynne R.
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K.
    Wong, Andrew
    Wrightl, Alan F.
    Zhang, Qunyuan
    Brennan, Eoin P.
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W.
    Eriksson, Per
    Franco-Cereceda, Anders
    Gadin, Jesper R.
    Gharavi, Ali G.
    Goddard, Michael E.
    Handsaker, Robert E.
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P.
    Ma, Baoshan
    McCarroll, Steven A.
    McKnight, Amy J.
    Min, Josine L.
    Moffatt, Miriam F.
    Montgomery, Grant W.
    Murabito, Joanne M.
    Nicholson, George
    Nyholt, Dale R.
    Okada, Yukinori
    Perry, John R. B.
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M.
    Sandholm, Niina
    Scott, Robert A.
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    van 't Hooft, Ferdinand M.
    Vinkhuyzen, Anna A. E.
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T.
    Heath, Andrew C.
    Arveiler, Dominique
    Bakker, Stephan J. L.
    Beilby, John
    Bergman, Richard N.
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J.
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Crawford, Dana C.
    Cupples, L. Adrienne
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M.
    Dominiczak, Anna F.
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G.
    Farrall, Martin
    Felix, Stephan B.
    Ferrannini, Ele
    Ferrieres, Jean
    Ford, Ian
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Gansevoort, Ron T.
    Gejman, Pablo V.
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hall, Alistair S.
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hicks, Andrew A.
    Hindorff, Lucia A.
    Hingorani, Aroon D.
    Hofman, Albert
    Homuth, Georg
    Hovingh, G. Kees
    Humphries, Steve E.
    Hunt, Steven C.
    Hypponen, Elina
    Illig, Thomas
    Jacobs, Kevin B.
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Jukema, J. Wouter
    Jula, Antti M.
    Kaprio, Jaakko
    Kastelein, John J. P.
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Knekt, Paul
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T.
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A.
    Langenberg, Claudia
    Le Marchand, Laic
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Mannisto, Satu
    Marette, Andre
    Matise, Tara C.
    McKenzie, Colin A.
    McKnight, Barbara
    Moll, Frans L.
    Morris, Andrew D.
    Morris, Andrew P.
    Murray, Jeffrey C.
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ong, Ken K.
    Madden, Pamela A. F.
    Pasterkamp, Gerard
    Peden, John F.
    Peters, Annette
    Postma, Dirkje S.
    Pramstaller, Peter P.
    Price, Jackie F.
    Qi, Lu
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rao, D. C.
    Rice, Treva K.
    Ridker, Paul M.
    Rioux, John D.
    Ritchie, Marylyn D.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Saramines, Jouko
    Sarzynski, Mark A.
    Schunkert, Heribert
    Schwarz, Peter E. H.
    Sever, Peter
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stolk, Ronald P.
    Strauch, Konstantin
    Toenjes, Anke
    Tregouet, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Voelker, Uwe
    Waeber, Gerard
    Willemsen, Gonneke
    Witteman, Jacqueline C.
    Zillikens, M. Carola
    Adair, Linda S.
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Assimes, Themistocles L.
    Bochud, Murielle
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Bornstein, Stefan R.
    Bottinger, Erwin P.
    Bouchard, Claude
    Cauchi, Stephane
    Chambers, John C.
    Chanock, Stephen J.
    Cooper, Richard S.
    de Bakker, Paul I. W.
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Froguel, Philippe
    Groop, Leif C.
    Haiman, Christopher A.
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J.
    Hveem, Kristian
    Kaplan, Robert C.
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G.
    Maerz, Winfried
    Melbve, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B.
    Njolstad, Inger
    Oostra, Ben A.
    Palmer, Colin N. A.
    Pedersen, Nancy L.
    Perola, Markus
    Perusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E.
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E.
    Schlessinger, David
    Slagboom, P. Eline
    Snieder, Harold
    Spector, Tim D.
    Thorsteinsdottir, Unnu R.
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wichmann, H-Erich
    Wilson, James F.
    Zanen, Pieter
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Heid, Iris M.
    O'Connell, Jeffrey R.
    Strachan, David P.
    Stefansson, Kari
    van Duijri, Cornelia M.
    Abecasis, Goncalo R.
    Franke, Lude
    Frayling, Timothy M.
    McCarthy, Mark I.
    Visscher, Peter M.
    Scherag, Andre
    Willer, Cristen J.
    Boehnke, Michael
    Mohlke, Karen L.
    Lindgren, Cecilia M.
    Beckmann, Jacques S.
    Barroso, Ines
    North, Kari E.
    Ingelsson, Erik
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Speliotes, Elizabeth K.
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, 197-U401 p.Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 9. Lu, Yingchang
    et al.
    Day, Felix R.
    Gustafsson, Stefan
    Buchkovich, Martin L.
    Na, Jianbo
    Bataille, Veronique
    Cousminer, Diana L.
    Dastani, Zari
    Drong, Alexander W.
    Esko, Tonu
    Evans, David M.
    Falchi, Mario
    Feitosa, Mary F.
    Ferreira, Teresa
    Hedman, Asa K.
    Haring, Robin
    Hysi, Pirro G.
    Iles, Mark M.
    Justice, Anne E.
    Kanoni, Stavroula
    Lagou, Vasiliki
    Li, Rui
    Li, Xin
    Locke, Adam
    Lu, Chen
    Magi, Reedik
    Perry, John R. B.
    Pers, Tune H.
    Qi, Qibin
    Sanna, Marianna
    Schmidt, Ellen M.
    Scott, William R.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Lund University Diabetes Centre, Department of Clinical Science, Genetic and Molecular Epidemiology Unit, Skåne University Hosptial, 205 02 Malmö, Sweden.
    Teumer, Alexander
    Vinkhuyzen, Anna A. E.
    Walker, Ryan W.
    Westra, Harm-Jan
    Zhang, Mingfeng
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Zhihong
    Afzal, Uzma
    Ahluwalia, Tarunveer Singh
    Bakker, Stephan J. L.
    Bellis, Claire
    Bonnefond, Amelie
    Borodulin, Katja
    Buchman, Aron S.
    Cederholm, Tommy
    Choh, Audrey C.
    Choi, Hyung Jin
    Curran, Joanne E.
    de Groot, Lisette C. P. G. M.
    De Jager, Philip L.
    Dhonukshe-Rutten, Rosalie A. M.
    Enneman, Anke W.
    Eury, Elodie
    Evans, Daniel S.
    Forsen, Tom
    Friedrich, Nele
    Fumeron, Frederic
    Garcia, Melissa E.
    Gartner, Simone
    Han, Bok-Ghee
    Havulinna, Aki S.
    Hayward, Caroline
    Hernandez, Dena
    Hillege, Hans
    Ittermann, Till
    Kent, Jack W.
    Kolcic, Ivana
    Laatikainen, Tiina
    Lahti, Jari
    Leach, Irene Mateo
    Lee, Christine G.
    Lee, Jong-Young
    Liu, Tian
    Liu, Youfang
    Lobbens, Stephane
    Loh, Marie
    Lyytikainen, Leo-Pekka
    Medina-Gomez, Carolina
    Michaelsson, Karl
    Nalls, Mike A.
    Nielson, Carrie M.
    Oozageer, Laticia
    Pascoe, Laura
    Paternoster, Lavinia
    Polasek, Ozren
    Ripatti, Samuli
    Sarzynski, Mark A.
    Shin, Chan Soo
    Narancic, Nina Smolej
    Spira, Dominik
    Srikanth, Priya
    Steinhagen-Thiessen, Elisabeth
    Sung, Yun Ju
    Swart, Karin M. A.
    Taittonen, Leena
    Tanaka, Toshiko
    Tikkanen, Emmi
    van der Velde, Nathalie
    van Schoor, Natasja M.
    Verweij, Niek
    Wright, Alan F.
    Yu, Lei
    Zmuda, Joseph M.
    Eklund, Niina
    Forrester, Terrence
    Grarup, Niels
    Jackson, Anne U.
    Kristiansson, Kati
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Lichtner, Peter
    Luan, Jian'an
    Mahajan, Anubha
    Mannisto, Satu
    Palmer, Cameron D.
    Ried, Janina S.
    Scott, Robert A.
    Stancakova, Alena
    Wagner, Peter J.
    Demirkan, Ayse
    Doring, Angela
    Gudnason, Vilmundur
    Kiel, Douglas P.
    Kuhnel, Brigitte
    Mangino, Massimo
    Mcknight, Barbara
    Menni, Cristina
    O'Connell, Jeffrey R.
    Oostra, Ben A.
    Shuldiner, Alan R.
    Song, Kijoung
    Vandenput, Liesbeth
    van Duijn, Cornelia M.
    Vollenweider, Peter
    White, Charles C.
    Boehnke, Michael
    Boettcher, Yvonne
    Cooper, Richard S.
    Forouhi, Nita G.
    Gieger, Christian
    Grallert, Harald
    Hingorani, Aroon
    Jorgensen, Torben
    Jousilahti, Pekka
    Kivimaki, Mika
    Kumari, Meena
    Laakso, Markku
    Langenberg, Claudia
    Linneberg, Allan
    Luke, Amy
    Mckenzie, Colin A.
    Palotie, Aarno
    Pedersen, Oluf
    Peters, Annette
    Strauch, Konstantin
    Tayo, Bamidele O.
    Wareham, Nicholas J.
    Bennett, David A.
    Bertram, Lars
    Blangero, John
    Bluher, Matthias
    Bouchard, Claude
    Campbell, Harry
    Cho, Nam H.
    Cummings, Steven R.
    Czerwinski, Stefan A.
    Demuth, Ilja
    Eckardt, Rahel
    Eriksson, Johan G.
    Ferrucci, Luigi
    Franco, Oscar H.
    Froguel, Philippe
    Gansevoort, Ron T.
    Hansen, Torben
    Harris, Tamara B.
    Hastie, Nicholas
    Heliovaara, Markku
    Hofman, Albert
    Jordan, Joanne M.
    Jula, Antti
    Kahonen, Mika
    Kajantie, Eero
    Knekt, Paul B.
    Koskinen, Seppo
    Kovacs, Peter
    Lehtimaki, Terho
    Lind, Lars
    Liu, Yongmei
    Orwoll, Eric S.
    Osmond, Clive
    Perola, Markus
    Perusse, Louis
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rao, D. C.
    Rice, Treva K.
    Rivadeneira, Fernando
    Rudan, Igor
    Salomaa, Veikko
    Sorensen, Thorkild I. A.
    Stumvoll, Michael
    Tonjes, Anke
    Towne, Bradford
    Tranah, Gregory J.
    Tremblay, Angelo
    Uitterlinden, Andre G.
    van der Harst, Pim
    Vartiainen, Erkki
    Viikari, Jorma S.
    Vitart, Veronique
    Vohl, Marie-Claude
    Volzke, Henry
    Walker, Mark
    Wallaschofski, Henri
    Wild, Sarah
    Wilson, James F.
    Yengo, Loic
    Bishop, D. Timothy
    Borecki, Ingrid B.
    Chambers, John C.
    Cupples, L. Adrienne
    Dehghan, Abbas
    Deloukas, Panos
    Fatemifar, Ghazaleh
    Fox, Caroline
    Furey, Terrence S.
    Franke, Lude
    Han, Jiali
    Hunter, David J.
    Karjalainen, Juha
    Karpe, Fredrik
    Kaplan, Robert C.
    Kooner, Jaspal S.
    McCarthy, Mark I.
    Murabito, Joanne M.
    Morris, Andrew P.
    Bishop, Julia A. N.
    North, Kari E.
    Ohlsson, Claes
    Ong, Ken K.
    Prokopenko, Inga
    Richards, J. Brent
    Schadt, Eric E.
    Spector, Tim D.
    Widen, Elisabeth
    Willer, Cristen J.
    Yang, Jian
    Ingelsson, Erik
    Mohlke, Karen L.
    Hirschhorn, Joel N.
    Pospisilik, John Andrew
    Zillikens, M. Carola
    Lindgren, Cecilia
    Kilpelainen, Tuomas Oskari
    Loos, Ruth J. F.
    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, 10495Article in journal (Refereed)
    Abstract [en]

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P < 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

  • 10. 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 University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Frayling, Timothy M.
    Froguel, Philippe
    Galan, Pilar
    de Geus, Eco
    Gigante, Bruna
    Glazer, Nicole L.
    Goel, Anuj
    Groop, Leif
    Gudnason, Vilmundur
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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 resistance2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 6, 659-669 p.Article in journal (Refereed)
    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.

  • 11. Naska, A
    et al.
    Orfanos, P
    Trichopoulou, A
    May, A M
    Overvad, K
    Jakobsen, M U
    Tjønneland, A
    Halkjær, J
    Fagherazzi, G
    Clavel-Chapelon, F
    Boutron-Ruault, M-C
    Rohrmann, S
    Hermann, S
    Steffen, A
    Haubrock, J
    Oikonomou, E
    Dilis, V
    Katsoulis, M
    Sacerdote, C
    Sieri, S
    Masala, G
    Tumino, R
    Mattiello, A
    Bueno-de-Mesquita, H B
    Skeie, G
    Engeset, D
    Barricarte, A
    Rodríguez, L
    Dorronsoro, M
    Sánchez, M-J
    Chirlaque, M-D
    Agudo, A
    Manjer, J
    Wirfält, E
    Hellström, Veronica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Khaw, K-T
    Wareham, N J
    Spencer, E A
    Freisling, H
    Slimani, N
    Vergnaud, A-C
    Mouw, T
    Romaguera, D
    Odysseos, A
    Peeters, P H M
    Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study.2011In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 35, no 3, 416-426 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    SUBJECTS: This study included a representative sample of 24,310 randomly selected EPIC participants.

    METHODS: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders.

    RESULTS: In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (β=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (β=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake.

    CONCLUSION: Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.

  • 12. Palmerini, Elisabetta
    et al.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, Sergi
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Coronary calcification with no flow limiting lesions: a potential cause for ischaemic dysfunction in syndrome X patients2015In: IJC Heart and Vasculature, ISSN 2352-9067, Vol. 9, 109-114 p.Article in journal (Refereed)
    Abstract [en]

    Aim

    Exertional angina in patients with no coronary flow limiting lesions remains a clinical puzzle. We aimed to assess the extent of coronary artery calcification (CAC) and its relationship to ventricular wall motion function using stress echocardiography in a group of patients limited by exertional angina, but no obstructive lesions.

    Methods

    We compared CT coronary calcium score (CACS) and dobutamine stress echocardiography in 55 patients (age 64.7 ± 7.7 years), divided into Group 1 (CACS ≤ 100) and Group 2 (CACS > 100). No patient had LV ejection fraction-EF < 55%, pulmonary hypertension, arrhythmia, renal failure or parathyroid disease. Multiple linear regression analysis was used to test the association between gender-standardized continuous echocardiographic parameters and patient groups adjusted for age, body surface area, osteoporosis and CV risk factors and CACS.

    Results

    At rest, LV long axis ‘subendocardial’ function was reduced (amplitude: β − 1.11 SD, p < 0.05, R2 0.6 and systolic velocity: β − 1.08 SD, p < 0.05, R2 0.44), left atrial (LA) indexed volume was raised (β 1.06 SD, p < 0.05, R2 0.37) and its systolic velocity decreased (β − 1.05 SD, p < 0.05, R2 0.35) in Group 2. With stress, wall motion score index increased (p < 0.05) and long axis disturbances worsened only in the same group. Multivariate analysis demonstrated clear relationship between ischaemic LV disturbances, reduced long axis amplitude, global longitudinal systolic strain and early diastolic strain rate. Resting and stress RV lengthening velocity also correlated with CAC score.

    Conclusion

    In symptomatic patients with no obstructive coronary lesions and with more than mild CAC, long axis disturbances and wall motion score index rise occur with stress, at the time of symptom development and correlate with severity of arterial calcification. These findings suggest CAC as a potential mechanism for coronary wall stiffness and consequently exertional ischaemic changes as a result of limited flow reserve.

  • 13. Randall, Joshua C
    et al.
    Winkler, Thomas W
    Kutalik, Zoltán
    Berndt, Sonja I
    Jackson, Anne U
    Monda, Keri L
    Kilpeläinen, Tuomas O
    Esko, Tõnu
    Mägi, Reedik
    Li, Shengxu
    Workalemahu, Tsegaselassie
    Feitosa, Mary F
    Croteau-Chonka, Damien C
    Day, Felix R
    Fall, Tove
    Ferreira, Teresa
    Gustafsson, Stefan
    Locke, Adam E
    Mathieson, Iain
    Scherag, Andre
    Vedantam, Sailaja
    Wood, Andrew R
    Liang, Liming
    Steinthorsdottir, Valgerdur
    Thorleifsson, Gudmar
    Dermitzakis, Emmanouil T
    Dimas, Antigone S
    Karpe, Fredrik
    Min, Josine L
    Nicholson, George
    Clegg, Deborah J
    Person, Thomas
    Krohn, Jon P
    Bauer, Sabrina
    Buechler, Christa
    Eisinger, Kristina
    Bonnefond, Amélie
    Froguel, Philippe
    Hottenga, Jouke-Jan
    Prokopenko, Inga
    Waite, Lindsay L
    Harris, Tamara B
    Smith, Albert Vernon
    Shuldiner, Alan R
    McArdle, Wendy L
    Caulfield, Mark J
    Munroe, Patricia B
    Grönberg, Henrik
    Chen, Yii-Der Ida
    Li, Guo
    Beckmann, Jacques S
    Johnson, Toby
    Thorsteinsdottir, Unnur
    Teder-Laving, Maris
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Zhao, Jing Hua
    Amin, Najaf
    Oostra, Ben A
    Kraja, Aldi T
    Province, Michael A
    Cupples, L Adrienne
    Heard-Costa, Nancy L
    Kaprio, Jaakko
    Ripatti, Samuli
    Surakka, Ida
    Collins, Francis S
    Saramies, Jouko
    Tuomilehto, Jaakko
    Jula, Antti
    Salomaa, Veikko
    Erdmann, Jeanette
    Hengstenberg, Christian
    Loley, Christina
    Schunkert, Heribert
    Lamina, Claudia
    Wichmann, H Erich
    Albrecht, Eva
    Gieger, Christian
    Hicks, Andrew A
    Johansson, Asa
    Pramstaller, Peter P
    Kathiresan, Sekar
    Speliotes, Elizabeth K
    Penninx, Brenda
    Hartikainen, Anna-Liisa
    Jarvelin, Marjo-Riitta
    Gyllensten, Ulf
    Boomsma, Dorret I
    Campbell, Harry
    Wilson, James F
    Chanock, Stephen J
    Farrall, Martin
    Goel, Anuj
    Medina-Gomez, Carolina
    Rivadeneira, Fernando
    Estrada, Karol
    Uitterlinden, André G
    Hofman, Albert
    Zillikens, M Carola
    den Heijer, Martin
    Kiemeney, Lambertus A
    Maschio, Andrea
    Hall, Per
    Tyrer, Jonathan
    Teumer, Alexander
    Völzke, Henry
    Kovacs, Peter
    Tönjes, Anke
    Mangino, Massimo
    Spector, Tim D
    Hayward, Caroline
    Rudan, Igor
    Hall, Alistair S
    Samani, Nilesh J
    Attwood, Antony Paul
    Sambrook, Jennifer G
    Hung, Joseph
    Palmer, Lyle J
    Lokki, Marja-Liisa
    Sinisalo, Juha
    Boucher, Gabrielle
    Huikuri, Heikki
    Lorentzon, Mattias
    Ohlsson, Claes
    Eklund, Niina
    Eriksson, Johan G
    Barlassina, Cristina
    Rivolta, Carlo
    Nolte, Ilja M
    Snieder, Harold
    Van der Klauw, Melanie M
    Van Vliet-Ostaptchouk, Jana V
    Gejman, Pablo V
    Shi, Jianxin
    Jacobs, Kevin B
    Wang, Zhaoming
    Bakker, Stephan J L
    Mateo Leach, Irene
    Navis, Gerjan
    van der Harst, Pim
    Martin, Nicholas G
    Medland, Sarah E
    Montgomery, Grant W
    Yang, Jian
    Chasman, Daniel I
    Ridker, Paul M
    Rose, Lynda M
    Lehtimäki, Terho
    Raitakari, Olli
    Absher, Devin
    Iribarren, Carlos
    Basart, Hanneke
    Hovingh, Kees G
    Hyppönen, Elina
    Power, Chris
    Anderson, Denise
    Beilby, John P
    Hui, Jennie
    Jolley, Jennifer
    Sager, Hendrik
    Bornstein, Stefan R
    Schwarz, Peter E H
    Kristiansson, Kati
    Perola, Markus
    Lindström, Jaana
    Swift, Amy J
    Uusitupa, Matti
    Atalay, Mustafa
    Lakka, Timo A
    Rauramaa, Rainer
    Bolton, Jennifer L
    Fowkes, Gerry
    Fraser, Ross M
    Price, Jackie F
    Fischer, Krista
    Krjutå Kov, Kaarel
    Metspalu, Andres
    Mihailov, Evelin
    Langenberg, Claudia
    Luan, Jian'an
    Ong, Ken K
    Chines, Peter S
    Keinanen-Kiukaanniemi, Sirkka M
    Saaristo, Timo E
    Edkins, Sarah
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Morris, Andrew David
    Palmer, Colin N A
    Erbel, Raimund
    Moebus, Susanne
    Nöthen, Markus M
    Pechlivanis, Sonali
    Hveem, Kristian
    Narisu, Narisu
    Hamsten, Anders
    Humphries, Steve E
    Strawbridge, Rona J
    Tremoli, Elena
    Grallert, Harald
    Thorand, Barbara
    Illig, Thomas
    Koenig, Wolfgang
    Müller-Nurasyid, Martina
    Peters, Annette
    Boehm, Bernhard O
    Kleber, Marcus E
    März, Winfried
    Winkelmann, Bernhard R
    Kuusisto, Johanna
    Laakso, Markku
    Arveiler, Dominique
    Cesana, Giancarlo
    Kuulasmaa, Kari
    Virtamo, Jarmo
    Yarnell, John W G
    Kuh, Diana
    Wong, Andrew
    Lind, Lars
    de Faire, Ulf
    Gigante, Bruna
    Magnusson, Patrik K E
    Pedersen, Nancy L
    Dedoussis, George
    Dimitriou, Maria
    Kolovou, Genovefa
    Kanoni, Stavroula
    Stirrups, Kathleen
    Bonnycastle, Lori L
    Njølstad, Inger
    Wilsgaard, Tom
    Ganna, Andrea
    Rehnberg, Emil
    Hingorani, Aroon
    Kivimaki, Mika
    Kumari, Meena
    Assimes, Themistocles L
    Barroso, Inês
    Boehnke, Michael
    Borecki, Ingrid B
    Deloukas, Panos
    Fox, Caroline S
    Frayling, Timothy
    Groop, Leif C
    Haritunians, Talin
    Hunter, David
    Ingelsson, Erik
    Kaplan, Robert
    Mohlke, Karen L
    O'Connell, Jeffrey R
    Schlessinger, David
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Abecasis, Gonçalo R
    McCarthy, Mark I
    Hirschhorn, Joel N
    Qi, Lu
    Loos, Ruth J F
    Lindgren, Cecilia M
    North, Kari E
    Heid, Iris M
    Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits2013In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 6, e1003500- p.Article in journal (Refereed)
    Abstract [en]

    Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

  • 14.
    Renström, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Florez, Jose C
    Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hu, Frank B
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Genetic predisposition to long-term nondiabetic deteriorations in glucose homeostasis: Ten-year follow-up of the GLACIER study.2011In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 1, 345-54 p.Article in journal (Refereed)
    Abstract [en]

    Our findings imply that genetic profiling might facilitate the early detection of persons who are genetically susceptible to deteriorating glucose control; studies of incident type 2 diabetes and discrete cardiovascular end points will help establish whether the magnitude of these changes is clinically relevant.

  • 15. Scott, Robert A
    et al.
    Chu, Audrey Y
    Grarup, Niels
    Manning, Alisa K
    Hivert, Marie-France
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tönjes, Anke
    Yesupriya, Ajay
    Barnes, Daniel
    Bouatia-Naji, Nabila
    Glazer, Nicole L
    Jackson, Anne U
    Kutalik, Zoltán
    Lagou, Vasiliki
    Marek, Diana
    Rasmussen-Torvik, Laura J
    Stringham, Heather M
    Tanaka, Toshiko
    Aadahl, Mette
    Arking, Dan E
    Bergmann, Sven
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Bornstein, Stefan R
    Brunner, Eric
    Bumpstead, Suzannah J
    Brage, Soren
    Carlson, Olga D
    Chen, Han
    Chen, Yii-Der Ida
    Chines, Peter S
    Collins, Francis S
    Couper, David J
    Dennison, Elaine M
    Dowling, Nicole F
    Egan, Josephine S
    Ekelund, Ulf
    Erdos, Michael R
    Forouhi, Nita G
    Fox, Caroline S
    Goodarzi, Mark O
    Grässler, Jürgen
    Gustafsson, Stefan
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hansen, Torben
    Hingorani, Aroon
    Holloway, John W
    Hu, Frank B
    Isomaa, Bo
    Jameson, Karen A
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Jonsson, Anna
    Jørgensen, Torben
    Kivimaki, Mika
    Kovacs, Peter
    Kumari, Meena
    Kuusisto, Johanna
    Laakso, Markku
    Lecoeur, Cécile
    Lévy-Marchal, Claire
    Li, Guo
    Loos, Ruth J F
    Lyssenko, Valeri
    Marmot, Michael
    Marques-Vidal, Pedro
    Morken, Mario A
    Müller, Gabriele
    North, Kari E
    Pankow, James S
    Payne, Felicity
    Prokopenko, Inga
    Psaty, Bruce M
    Renström, Frida
    Rice, Ken
    Rotter, Jerome I
    Rybin, Denis
    Sandholt, Camilla H
    Sayer, Avan A
    Shrader, Peter
    Schwarz, Peter E H
    Siscovick, David S
    Stancáková, Alena
    Stumvoll, Michael
    Teslovich, Tanya M
    Waeber, Gérard
    Williams, Gordon H
    Witte, Daniel R
    Wood, Andrew R
    Xie, Weijia
    Boehnke, Michael
    Cooper, Cyrus
    Ferrucci, Luigi
    Froguel, Philippe
    Groop, Leif
    Kao, W H Linda
    Vollenweider, Peter
    Walker, Mark
    Watanabe, Richard M
    Pedersen, Oluf
    Meigs, James B
    Ingelsson, Erik
    Barroso, Inês
    Florez, Jose C
    Franks, Paul W
    Dupuis, Josée
    Wareham, Nicholas J
    Langenberg, Claudia
    No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels2012In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 61, no 5, 1291-1296 p.Article in journal (Refereed)
    Abstract [en]

    Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-gram glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × Physical Activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

  • 16. Scott, Robert A.
    et al.
    Lagou, Vasiliki
    Welch, Ryan P.
    Wheeler, Eleanor
    Montasser, May E.
    Luan, Jian'an
    Maegi, Reedik
    Strawbridge, Rona J.
    Rehnberg, Emil
    Gustafsson, Stefan
    Kanoni, Stavroula
    Rasmussen-Torvik, Laura J.
    Yengo, Loic
    Lecoeur, Cecile
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sanna, Serena
    Sidore, Carlo
    Johnson, Paul C. D.
    Jukema, J. Wouter
    Johnson, Toby
    Mahajan, Anubha
    Verweij, Niek
    Thorleifsson, Gudmar
    Hottenga, Jouke-Jan
    Shah, Sonia
    Smith, Albert V.
    Sennblad, Bengt
    Gieger, Christian
    Salo, Perttu
    Perola, Markus
    Timpson, Nicholas J.
    Evans, David M.
    St Pourcain, Beate
    Wu, Ying
    Andrews, Jeanette S.
    Hui, Jennie
    Bielak, Lawrence F.
    Zhao, Wei
    Horikoshi, Momoko
    Navarro, Pau
    Isaacs, Aaron
    O'Connell, Jeffrey R.
    Stirrups, Kathleen
    Vitart, Veronique
    Hayward, Caroline
    Esko, Tonu
    Mihailov, Evelin
    Fraser, Ross M.
    Fall, Tove
    Voight, Benjamin F.
    Raychaudhuri, Soumya
    Chen, Han
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Rayner, Nigel W.
    Robertson, Neil
    Rybin, Denis
    Liu, Ching-Ti
    Beckmann, Jacques S.
    Willems, Sara M.
    Chines, Peter S.
    Jackson, Anne U.
    Kang, Hyun Min
    Stringham, Heather M.
    Song, Kijoung
    Tanaka, Toshiko
    Peden, John F.
    Goel, Anuj
    Hicks, Andrew A.
    An, Ping
    Mueller-Nurasyid, Martina
    Franco-Cereceda, Anders
    Folkersen, Lasse
    Marullo, Letizia
    Jansen, Hanneke
    Oldehinkel, Albertine J.
    Bruinenberg, Marcel
    Pankow, James S.
    North, Kari E.
    Forouhi, Nita G.
    Loos, Ruth J. F.
    Edkins, Sarah
    Varga, Tibor V.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Oksa, Heikki
    Antonella, Mulas
    Nagaraja, Ramaiah
    Trompet, Stella
    Ford, Ian
    Bakker, Stephan J. L.
    Kong, Augustine
    Kumari, Meena
    Gigante, Bruna
    Herder, Christian
    Munroe, Patricia B.
    Caulfield, Mark
    Antti, Jula
    Mangino, Massimo
    Small, Kerrin
    Miljkovic, Iva
    Liu, Yongmei
    Atalay, Mustafa
    Kiess, Wieland
    James, Alan L.
    Rivadeneira, Fernando
    Uitterlinden, Andre G.
    Palmer, Colin N. A.
    Doney, Alex S. F.
    Willemsen, Gonneke
    Smit, Johannes H.
    Campbell, Susan
    Polasek, Ozren
    Bonnycastle, Lori L.
    Hercberg, Serge
    Dimitriou, Maria
    Bolton, Jennifer L.
    Fowkes, Gerard R.
    Kovacs, Peter
    Lindstrom, Jaana
    Zemunik, Tatijana
    Bandinelli, Stefania
    Wild, Sarah H.
    Basart, Hanneke V.
    Rathmann, Wolfgang
    Grallert, Harald
    Maerz, Winfried
    Kleber, Marcus E.
    Boehm, Bernhard O.
    Peters, Annette
    Pramstaller, Peter P.
    Province, Michael A.
    Borecki, Ingrid B.
    Hastie, Nicholas D.
    Rudan, Igor
    Campbell, Harry
    Watkins, Hugh
    Farrall, Martin
    Stumvoll, Michael
    Ferrucci, Luigi
    Waterworth, Dawn M.
    Bergman, Richard N.
    Collins, Francis S.
    Tuomilehto, Jaakko
    Watanabe, Richard M.
    de Geus, Eco J. C.
    Penninx, Brenda W.
    Hofman, Albert
    Oostra, Ben A.
    Psaty, Bruce M.
    Vollenweider, Peter
    Wilson, James F.
    Wright, Alan F.
    Hovingh, G. Kees
    Metspalu, Andres
    Uusitupa, Matti
    Magnusson, Patrik K. E.
    Kyvik, Kirsten O.
    Kaprio, Jaakko
    Price, Jackie F.
    Dedoussis, George V.
    Deloukas, Panos
    Meneton, Pierre
    Lind, Lars
    Boehnke, Michael
    Shuldiner, Alan R.
    van Duijn, Cornelia M.
    Morris, Andrew D.
    Toenjes, Anke
    Peyser, Patricia A.
    Beilby, John P.
    Koerner, Antje
    Kuusisto, Johanna
    Laakso, Markku
    Bornstein, Stefan R.
    Schwarz, Peter E. H.
    Lakka, Timo A.
    Rauramaa, Rainer
    Adair, Linda S.
    Smith, George Davey
    Spector, Tim D.
    Illig, Thomas
    de Faire, Ulf
    Hamsten, Anders
    Gudnason, Vilmundur
    Kivimaki, Mika
    Hingorani, Aroon
    Keinanen-Kiukaanniemi, Sirkka M.
    Saaristo, Timo E.
    Boomsma, Dorret I.
    Stefansson, Kari
    van der Harst, Pim
    Dupuis, Josee
    Pedersen, Nancy L.
    Sattar, Naveed
    Harris, Tamara B.
    Cucca, Francesco
    Ripatti, Samuli
    Salomaa, Veikko
    Mohlke, Karen L.
    Balkau, Beverley
    Froguel, Philippe
    Pouta, Anneli
    Jarvelin, Marjo-Riitta
    Wareham, Nicholas J.
    Bouatia-Naji, Nabila
    McCarthy, Mark I.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Meigs, James B.
    Teslovich, Tanya M.
    Florez, Jose C.
    Langenberg, Claudia
    Ingelsson, Erik
    Prokopenko, Inga
    Barroso, Ines
    Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 9, 991-1005 p.Article in journal (Refereed)
    Abstract [en]

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

  • 17.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Interplay between genetics and environment in obesity2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. Being one of the largest current global health problems, obesity is a result of interplay between genetic and environmental factors. In this thesis we studied the genetic underpinning of adipose tissue distribution; investigated causality between obesity and periodontitis using instrumental variable analyses in genetic epidemiology settings; studied interactions between obesity-associated loci and physical activity on obesity; and checked if loci identified in genome-wide association studies are good candidates for gene-environment interactions using heterogeneity of variance analyses.

    Methods. In Paper 1 we performed a meta-analysis of large-scale genetic association studies for waist traits in 224,459 participants followed by a variety of statistical and bioinformatics methods to obtain insights into the biology of the underlying adipose distributions. In Paper 2 we used genetic variants associated with body mass index (BMI) as instruments within a Mendelian randomization framework to study causality between obesity and periodontitis in 49,066 participants. In Paper 3 we studied the interaction between an FTO single nucleotide polymorphism (SNP) rs9939609 and physical activity in obesity outcomes through meta-analysis of 237,434 participants. In Paper 4 we evaluated if SNPs established through main-effects meta-analysis of genome-wide association studies represent strong or weak candidates for gene-environment interactions, inferred by the degree of phenotypic heterogeneity across genotypes at a given SNP locus.

    Results. In Paper 1 we identified 49 loci (33 novel) associated with waist-to-hip ratio adjusted for BMI (P<5×10-8), 20 of which displayed significant sexual dimorphism, of which 19 displayed a stronger effect in women than in men. We also detected 19 additional loci newly associated with related waist and hip circumference measures. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insights into potential pathophysiological mechanisms. In Paper 2 we confirmed observational associations between BMI and periodontitis with a pooled odds ratio (OR) of 1.13 per standard deviation increase in BMI (95%CI:1.03, 1.24) in all participants and 1.25 (95%CI:1.10, 1.42) in participants with clinical data. The instrumental variable meta-analysis yielded an OR of 1.05 (95%CI:0.80, 1.38) per BMI standard deviation, and 0.90 (95%CI:0.56, 1.46) in participants with clinical data. In Paper 3 we showed that physical activity attenuates the influence of FTO variation in rs9939609 on obesity (Pinteraction=0.001) with the A allele of rs9939609 increasing the odds of obesity less in the physically active group, with a per-allele OR of 1.22 (95%CI:1.19, 1.25), than in the inactive group, with a per-allele OR of 1.30 (95%CI:1.24, 1.36). In Paper 4 we show that rank-ordered distributions of P-values between marginal effects genome-wide association studies (GWAS) and heterogeneity of variance analyses for all SNPs for BMI and lipid traits have very weak correlations for most traits (Spearman rho of 0.0034 for total cholesterol and 0.0044 for BMI for the squared phenotype residuals regression method) indicating that variants with strong marginal effects are in general poor candidates for gene-environment interactions based on heterogeneity of variance analyses, although a small number of variants convey strong marginal and variance effects, such as those at the FTO locus, meaning that they are likely to convey both marginal and interaction effects.

    Conclusion. The work outlined in this thesis sheds light on the complexity of genetic and environmental factors in obesity. We have identified novel loci associated with waist traits and described pathways implicated in adipose distribution. We have shown that based on Mendelian randomization analyses the association between periodontitis and obesity is unlikely to be causal. We have confirmed interactions between a bona-fide obesity locus (FTO) and physical activity on obesity and have shown that, in contrast to FTO, the majority of genetic variants identified through GWAS are unlikely to be good candidates for gene-environment interactions based on heterogeneity of variance analyses.

  • 18.
    Shungin, Dmitry
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University.
    Cornelis, Marilyn C.
    Divaris, Kimon
    Holtfreter, Birte
    Shaffer, John R.
    Yu, Yau-Hua
    Barros, Silvana P.
    Beck, James D.
    Biffar, Reiner
    Boerwinkle, Eric A.
    Crout, Richard J.
    Ganna, Andrea
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hindy, George
    Hu, Frank B.
    Kraft, Peter
    McNeil, Daniel W.
    Melander, Olle
    Moss, Kevin L.
    North, Kari E.
    Orho-Melander, Marju
    Pedersen, Nancy L.
    Ridker, Paul M.
    Rimm, Eric B.
    Rose, Lynda M.
    Rukh, Gull
    Teumer, Alexander
    Weyant, Robert J.
    Chasman, Daniel I.
    Joshipura, Kaumudi
    Kocher, Thomas
    Magnusson, Patrik K. E.
    Marazita, Mary L.
    Nilsson, Peter
    Offenbacher, Steve
    Smith, George Davey
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmer, Tom M.
    Timpson, Nicholas J.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium2015In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, no 2, 638-650 p.Article in journal (Refereed)
    Abstract [en]

    Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI: 1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.

  • 19.
    Shungin, Dmitry
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Alexandra Ioannidis
    Persson, Maurits
    Umeå University, Faculty of Medicine, Department of Odontology.
    Orthodontic treatment-related white spot lesions: a 14-year prospective quantitative follow-up, including bonding material assessment.2010In: American Journal of Orthodontics and Dentofacial Orthopedics, ISSN 0889-5406, E-ISSN 1097-6752, Vol. 138, no 2, 136.e1-8; discussion 136 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: White spots (WS) related to orthodontic treatment are severe cariologic and cosmetic complications, but they are shown to be partially reduced by remineralization or abrasion in short-term follow-ups. In this prospective study, we quantitatively analyzed changes in WS in general and in treatment-related white spot lesions (WSL) during orthodontic treatment and at a 12-year follow-up after treatment. In addition, we quantitatively compared the effects of an acrylic bonding material vs a glass ionomer cement (GIC) on WSL. METHODS: Sum areas of WS and WSL were calculated on scans of standardized photos of the vestibular surfaces of 4 teeth in consecutive orthodontic patients (median treatment time, 1.7 years) bonded with the 2 materials in a split-mouth design. Comparisons were made in 59 patients before treatment (BF), at debonding (T0), at 1 year (T1), and at 2 years (T2), and in 30 patients at a 12-year follow-up (T3) with the Friedman test followed by pairwise comparisons with the Wilcoxon matched-pairs signed rank test. Differences of the effects of acrylic vs GIC on the sum areas of WSL were tested for each observation period with the Mann-Whitney U test. RESULTS: Increases in the sum areas of WS and WSL from BF to T0 (P <0.001) were followed by significant decreases at T1 (P <0.001) and T2 (P <0.01 for WS; P <0.001 for WSL). Significant changes were also found in the sum areas for WS at T3 compared with T2 (P <0.01), but not for WSL (P = 0.328). The sum areas of WS and WSL at T3 did not return to BF levels (P <0.001). Sum areas of WSL were higher for surfaces bonded with acrylic compared with GIC for each observation period from BF to T2 (P >0.001), and from T2 to T3 (P >0.05). CONCLUSIONS: Although significantly reduced during the 12-year follow-up and significantly lower with the GIC than the acrylic material at bonding, WSL are a cariologic and cosmetic problem for many orthodontic patients.

  • 20.
    Shungin, Dmitry
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology.
    Winkler, Thomas W.
    Croteau-Chonka, Damien C.
    Ferreira, Teresa
    Lockes, Adam E.
    Maegi, Reedik
    Strawbridge, Rona J.
    Pers, Tune H.
    Fischer, Krista
    Justice, Anne E.
    Workalemahu, Tsegaselassie
    Wu, Joseph M. W.
    Buchkovich, Martin L.
    Heard-Costa, Nancy L.
    Roman, Tamara S.
    Drong, Alexander W.
    Song, Ci
    Gustafsson, Stefan
    Day, Felix R.
    Esko, Tonu
    Fall, Tove
    Kutalik, Zoltan
    Luan, Jian'an
    Randall, Joshua C.
    Scherag, Andre
    Vedantam, Sailaja
    Wood, Andrew R.
    Chen, Jin
    Fehrmann, Rudolf
    Karjalainen, Juha
    Kahali, Bratati
    Liu, Ching-Ti
    Schmidt, Ellen M.
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bragg-Gresham, Jennifer L.
    Buyske, Steven
    Demirkan, Ayse
    Ehret, Georg B.
    Feitosa, Mary F.
    Goel, Anuj
    Jackson, Anne U.
    Johnson, Toby
    Kleber, Marcus E.
    Kristiansson, Kati
    Mangino, Massimo
    Leach, Irene Mateo
    Medina-Gomez, Carolina
    Palmer, Cameron D.
    Pasko, Dorota
    Pechlivaniss, Sonali
    Peters, Marjolein J.
    Prokopenko, Inga
    Stancakova, Alena
    Sung, Yun Ju
    Tanakam, Toshiko
    Teumer, Alexander
    Van Vliet-Ostaptchouk, Jana V.
    Yengo, Loic
    Zhang, Weihua
    Albrecht, Eva
    Arnlov, Johan
    Arscott, Gillian M.
    Bandinelli, Stefania
    Barrett, Amy
    Bellis, Claire
    Bennett, Amanda J.
    Berne, Christian
    Blueher, Matthias
    Buhringer, Stefan
    Bonnet, Fabrice
    Boettcher, Yvonne
    Bruinenberg, Marcel
    Carba, Delia B.
    Caspersen, Ida H.
    Clarke, Robert
    Daw, E. Warwick
    Deelen, Joris
    Deelman, Ewa
    Delgado, Graciela
    Doney, Alex S. F.
    Eklund, Niina
    Erdos, Michael R.
    Estrada, Karol
    Eury, Elodie
    Friedrichs, Nele
    Garcia, Melissa E.
    Giedraitis, Vilmantas
    Gigante, Bruna
    Go, Alan S.
    Golay, Alain
    Grallert, Harald
    Grammer, Tanja B.
    Graessler, Juergen
    Grewal, Jagvir
    Groves, Christopher J.
    Haller, Toomas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hartman, Catharina A.
    Hassinen, Maija
    Hayward, Caroline
    Heikkila, Kauko
    Herzig, Karl-Heinz
    Helmer, Quinta
    Hillege, Hans L.
    Holmen, Oddgeir
    Hunt, Steven C.
    Isaacs, Aaron
    Ittermann, Till
    James, Alan L.
    Johansson, Ingegerd
    Juliusdottir, Thorhildur
    Kalafati, Ioanna-Panagiota
    Kinnunen, Leena
    Koenig, Wolfgang
    Kooner, Ishminder K.
    Kratzer, Wolfgang
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R.
    Lichtner, Peter
    Lind, Lars
    Lindstrom, Jaana
    Lobbens, Stephane
    Lorentzon, Mattias
    Mach, Francois
    Magnusson, Patrik K. E.
    Mahajan, Anubha
    McArdle, Wendy L.
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Mills, Rebecca
    Moayyeri, Alireza
    Monda, Ken L.
    Mooijaart, Simon P.
    Muehleisen, Thomas W.
    Mulas, Antonella
    Mueller, Gabriele
    Mueller-Nurasyid, Martina
    Nagaraja, Ramaiah
    Nalls, Michael A.
    Narisu, Narisu
    Glorioso, Nicola
    Nolte, Ilja M.
    Olden, Matthias
    Rayner, Nigel W.
    Renstrom, Frida
    Ried, Janina S.
    Robertson, Neil R.
    Rose, Lynda M.
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Sennblad, Bengt
    Seufferlein, Thomas
    Sitlani, Colleen M.
    Smith, Albert Vernon
    Stirrups, Kathleen
    Stringham, Heather M.
    Sundstrom, Johan
    Swertz, Morris A.
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tayo, Bamidele O.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tomaschitz, Andreas
    Troffa, Chiara
    van Oort, Floor V. A.
    Verweij, Niek
    Vonk, Judith M.
    Waite, Lindsay L.
    Wennauer, Roman
    Wilsgaard, Tom
    Wojczynski, Mary K.
    Wong, Andrew
    Zhang, Qunyuan
    Zhao, Jing Hua
    Brennan, Eoin P.
    Choi, Murim
    Eriksson, Per
    Folkersen, Lasse
    Franco-Cereceda, Anders
    Gharavi, Ali G.
    Hedman, Asa K.
    Hivert, Marie-France
    Huang, Jinyan
    Kanoni, Stavroula
    Karpe, Fredrik
    Keildson, Sarah
    Kiryluk, Krzysztof
    Liang, Liming
    Lifton, Richard P.
    Ma, Baoshan
    McKnight, Amy J.
    McPherson, Ruth
    Metspalu, Andres
    Min, Josine L.
    Moffatt, Miriam F.
    Montgomery, Grant W.
    Murabito, Joanne M.
    Nicholson, George
    Nyholt, Dale R.
    Olsson, Christian
    Perry, John R. B.
    Reinmaa, Eva
    Salem, Rany M.
    Sandholm, Niina
    Schadt, Eric E.
    Scott, Robert A.
    Stolk, Lisette
    Vallejo, Edgar E.
    Westra, Harm-Jan
    Zondervan, Krina T.
    Amouyel, Philippe
    Arveiler, Dominique
    Bakker, Stephan J. L.
    Beilby, John
    Bergman, Richard N.
    Blangero, John
    Brown, Morris J.
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chiness, Peter S.
    Claudi-Boehmi, Simone
    Collins, Francis S.
    Crawford, Dana C.
    Danesh, John
    de Faire, Ulf
    de Geusl, Eco J. C.
    Doerr, Marcus
    Erbel, Raimund
    Eriksson, Johan G.
    Farrall, Martin
    Ferrannini, Ele
    Ferrieres, Jean
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Gansevoort, Ron T.
    Gieger, Christian
    Gudnason, Vilmundur
    Haiman, Christopher A.
    Harris, Tamara B.
    Hattersley, Andrew T.
    Heliovaara, Markku
    Hicks, Andrew A.
    Hingorani, Aroon D.
    Hoffmann, Wolfgang
    Hofman, Albert
    Homuth, Georg
    Humphries, Steve E.
    Hyppoenen, Elina
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Johansen, Berit
    Jousilahti, Pekka
    Jula, Antti M.
    Kaprio, Jaakko
    Kee, Frank
    Keinanen-Kiukaanniemi, Sirkka M.
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T.
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Lakka, Timo A.
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Mannisto, Satu
    Marette, Andre
    Matise, Tara C.
    McKenzie, Colin A.
    McKnight, Barbara
    Musk, Arthur W.
    Mohlenkamp, Stefan
    Morris, Andrew D.
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ong, Ken K.
    Palmer, Lyle J.
    Penninx, Brenda W.
    Peters, Annette
    Pramstaller, Peter P.
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rao, D. C.
    Rice, Treva K.
    Ridker, Paul M.
    Ritchie, Marylyn D.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Saramies, Jouko
    Sarzynski, Mark A.
    Schwarz, Peter E. H.
    Shuldiner, Alan R.
    Staessen, Jan A.
    Steinthorsdottir, Valgerdur
    Stolk, Ronald P.
    Strauch, Konstantin
    Toenjes, Anke
    Tremblay, Angelo
    Tremoli, Elena
    Vohl, Marie-Claude
    Voelker, Uwe
    Vollenweider, Peter
    Wilson, James F.
    Witteman, Jacqueline C.
    Adair, Linda S.
    Bochud, Murielle
    Boehm, Bernhard O.
    Bornstein, Stefan R.
    Bouchard, Claude
    Cauchi, Stephane
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Cooper, Richard S.
    Dedoussis, George
    Ferrucci, Luigi
    Froguel, Philippe
    Grabe, Hans-Joergen
    Hamsten, Anders
    Hui, Jennie
    Hveem, Kristian
    Joeckel, Karl-Heinz
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Maerz, Winfried
    Munroe, Patricia B.
    Njolstad, Inger
    Oostra, Ben A.
    Palmer, Colin N. A.
    Pedersen, Nancy L.
    Perola, Markus
    Perusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E.
    Saleheen, Danish
    Sinisalo, Juha
    Slagboom, P. Eline
    Snieder, Harold
    Spector, Tim D.
    Thorsteinsdottir, Unnur R.
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Math
    van der Harst, Pim
    Veronesi, Giovanni
    Walker, Mark
    Wareham, Nicholas J.
    Watkins, Hugh
    Wichmann, H-Erich
    Abecasis, Goncalo R.
    Assimes, Themistocles L.
    Berndt, Sonja I.
    Boehnkes, Michael
    Borecki, Ingrid B.
    Deloukas, Panos
    Franke, Lude
    Frayling, Timothy M.
    Groop, Leif C.
    Hunter, David J.
    Kaplan, Robert C.
    O'Connell, Jeffrey R.
    Qi, Lu
    Schlessinger, David
    Strachan, David P.
    Stefansson, Kari
    van Dujin, Cornelia M.
    Willer, Cristen J.
    Visscher, Peter M.
    Yang, Jian
    Hirschhorn, Joel N.
    Zillikens, M. Carola
    McCarthy, Mark I.
    Speliotes, Elizabeth K.
    North, Kari E.
    Fox, Caroline S.
    Barroso, Ines
    Franks, Paul W.
    Ingelsson, Erik
    Heid, Iris M.
    Loos, Ruth J. F.
    Cupples, L. Adrienne
    Morris, Andrew P.
    Lindgren, Cecilia M.
    Mohlke, Karen L.
    New genetic loci link adipose and insulin biology to body fat distribution2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, 187-U378 p.Article in journal (Refereed)
    Abstract [en]

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

  • 21. Varga, Tibor V.
    et al.
    Sonestedt, Emily
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
    Koivula, Robert W.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Andersson Escher, Stefan
    Barroso, Ines
    Nilsson, Peter
    Melander, Olle
    Orho-Melander, Marju
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
    Genetic determinants of long-term changes in blood lipid concentrations: 10-year follow-up of the GLACIER study2014In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 6, e1004388- p.Article in journal (Refereed)
    Abstract [en]

    Recent genome-wide meta-analyses identified 157 loci associated with cross-sectional lipid traits. Here we tested whether these loci associate (singly and in trait-specific genetic risk scores [GRS]) with longitudinal changes in total cholesterol (TC) and triglyceride (TG) levels in a population-based prospective cohort from Northern Sweden (the GLACIER Study). We sought replication in a southern Swedish cohort (the MDC Study; N = 2,943). GLACIER Study participants (N = 6,064) were genotyped with the MetaboChip array. Up to 3,495 participants had 10-yr follow-up data available in the GLACIER Study. The TC- and TG-specific GRSs were strongly associated with change in lipid levels (beta = 0.02 mmol/l per effect allele per decade follow-up, P = 2.0x10(-11) for TC; beta = 0.02 mmol/l per effect allele per decade follow-up, P = 5.0x10(-5) for TG). In individual SNP analysis, one TC locus, apolipoprotein E (APOE) rs4420638 (beta = 0.12 mmol/l per effect allele per decade follow-up, P = 2.0x10(-5)), and two TG loci, tribbles pseudokinase 1 (TRIB1) rs2954029 (beta = 0.09 mmol/l per effect allele per decade follow-up, P = 5.1x10(-4)) and apolipoprotein A-I (APOA1) rs6589564 (beta = 0.31 mmol/l per effect allele per decade follow-up, P = 1.4x10(-8)), remained significantly associated with longitudinal changes for the respective traits after correction for multiple testing. An additional 12 loci were nominally associated with TC or TG changes. In replication analyses, the APOE rs4420638, TRIB1 rs2954029, and APOA1 rs6589564 associations were confirmed (P <= 0.001). In summary, trait-specific GRSs are robustly associated with 10-yr changes in lipid levels and three individual SNPs were strongly associated with 10-yr changes in lipid levels.

  • 22. Wen, Wanqing
    et al.
    Kato, Norihiro
    Hwang, Joo-Yeon
    Guo, Xingyi
    Tabara, Yasuharu
    Li, Huaixing
    Dorajoo, Rajkumar
    Yang, Xiaobo
    Tsai, Fuu-Jen
    Li, Shengxu
    Wu, Ying
    Wu, Tangchun
    Kim, Soriul
    Guo, Xiuqing
    Liang, Jun
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adair, Linda S.
    Akiyama, Koichi
    Allison, Matthew
    Cai, Qiuyin
    Chang, Li-Ching
    Chen, Chien-Hsiun
    Chen, Yuan-Tsong
    Cho, Yoon Shin
    Choi, Bo Youl
    Gao, Yutang
    Go, Min Jin
    Gu, Dongfeng
    Han, Bok-Ghee
    He, Meian
    Hixson, James E.
    Hu, Yanling
    Huang, Tao
    Isono, Masato
    Jung, Keum Ji
    Kang, Daehee
    Kim, Young Jin
    Kita, Yoshikuni
    Lee, Juyoung
    Lee, Nanette R.
    Lee, Jeannette
    Wang, Yiqin
    Liu, Jian-Jun
    Long, Jirong
    Moon, Sanghoon
    Nakamura, Yasuyuki
    Nakatochi, Masahiro
    Ohnaka, Keizo
    Rao, Dabeeru
    Shi, Jiajun
    Sull, Jae Woong
    Tan, Aihua
    Ueshima, Hirotsugu
    Wu, Chen
    Xiang, Yong-Bing
    Yamamoto, Ken
    Yao, Jie
    Ye, Xingwang
    Yokota, Mitsuhiro
    Zhang, Xiaomin
    Zheng, Yan
    Qi, Lu
    Rotter, Jerome I.
    Jee, Sun Ha
    Lin, Dongxin
    Mohlke, Karen L.
    He, Jiang
    Mo, Zengnan
    Wu, Jer-Yuarn
    Tai, E. Shyong
    Lin, Xu
    Miki, Tetsuro
    Kim, Bong-Jo
    Takeuchi, Fumihiko
    Zheng, Wei
    Shu, Xiao-Ou
    Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 17958Article in journal (Refereed)
    Abstract [en]

    Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

  • 23. Willer, Cristen J.
    et al.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    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.
    Do, Ron
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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.
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Lunds universitet, Harvard University.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Kathiresan, Sekar
    Mohlke, Karen L.
    Ingelsson, Erik
    Abecasis, Goncalo R.
    Discovery and refinement of loci associated with lipid levels2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, 1274-+ p.Article in journal (Refereed)
    Abstract [en]

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

  • 24. Wood, Andrew R
    et al.
    Esko, Tonu
    Yang, Jian
    Vedantam, Sailaja
    Pers, Tune H
    Gustafsson, Stefan
    Chu, Audrey Y
    Estrada, Karol
    Luan, Jian'an
    Kutalik, Zoltán
    Amin, Najaf
    Buchkovich, Martin L
    Croteau-Chonka, Damien C
    Day, Felix R
    Duan, Yanan
    Fall, Tove
    Fehrmann, Rudolf
    Ferreira, Teresa
    Jackson, Anne U
    Karjalainen, Juha
    Lo, Ken Sin
    Locke, Adam E
    Mägi, Reedik
    Mihailov, Evelin
    Porcu, Eleonora
    Randall, Joshua C
    Scherag, André
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Winkler, Thomas W
    Workalemahu, Tsegaselassie
    Zhao, Jing Hua
    Absher, Devin
    Albrecht, Eva
    Anderson, Denise
    Baron, Jeffrey
    Beekman, Marian
    Demirkan, Ayse
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Fraser, Ross M
    Goel, Anuj
    Gong, Jian
    Justice, Anne E
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Lui, Julian C
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Nalls, Michael A
    Nyholt, Dale R
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Prokopenko, Inga
    Ried, Janina S
    Ripke, Stephan
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden.
    Stancáková, Alena
    Strawbridge, Rona J
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Afzal, Uzma
    Arnlöv, Johan
    Arscott, Gillian M
    Bandinelli, Stefania
    Barrett, Amy
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Blüher, Matthias
    Bolton, Jennifer L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Buckley, Brendan M
    Buyske, Steven
    Caspersen, Ida H
    Chines, Peter S
    Clarke, Robert
    Claudi-Boehm, Simone
    Cooper, Matthew
    Daw, E Warwick
    De Jong, Pim A
    Deelen, Joris
    Delgado, Graciela
    Denny, Josh C
    Dhonukshe-Rutten, Rosalie
    Dimitriou, Maria
    Doney, Alex S F
    Dörr, Marcus
    Eklund, Niina
    Eury, Elodie
    Folkersen, Lasse
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Go, Alan S
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    de Groot, Lisette C P G M
    Groves, Christopher J
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hannemann, Anke
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hemani, Gibran
    Henders, Anjali K
    Hillege, Hans L
    Hlatky, Mark A
    Hoffmann, Wolfgang
    Hoffmann, Per
    Holmen, Oddgeir
    Houwing-Duistermaat, Jeanine J
    Illig, Thomas
    Isaacs, Aaron
    James, Alan L
    Jeff, Janina
    Johansen, Berit
    Johansson, Asa
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Junttila, Juhani
    Kho, Abel N
    Kinnunen, Leena
    Klopp, Norman
    Kocher, Thomas
    Kratzer, Wolfgang
    Lichtner, Peter
    Lind, Lars
    Lindström, Jaana
    Lobbens, Stéphane
    Lorentzon, Mattias
    Lu, Yingchang
    Lyssenko, Valeriya
    Magnusson, Patrik K E
    Mahajan, Anubha
    Maillard, Marc
    McArdle, Wendy L
    McKenzie, Colin A
    McLachlan, Stela
    McLaren, Paul J
    Menni, Cristina
    Merger, Sigrun
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Narisu, Narisu
    Nauck, Matthias
    Nolte, Ilja M
    Nöthen, Markus M
    Oozageer, Laticia
    Pilz, Stefan
    Rayner, Nigel W
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden.
    Robertson, Neil R
    Rose, Lynda M
    Roussel, Ronan
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Schunkert, Heribert
    Scott, Robert A
    Sehmi, Joban
    Seufferlein, Thomas
    Shi, Jianxin
    Silventoinen, Karri
    Smit, Johannes H
    Smith, Albert Vernon
    Smolonska, Joanna
    Stanton, Alice V
    Stirrups, Kathleen
    Stott, David J
    Stringham, Heather M
    Sundström, Johan
    Swertz, Morris A
    Syvänen, Ann-Christine
    Tayo, Bamidele O
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    van Dijk, Suzanne
    van Schoor, Natasja M
    van der Velde, Nathalie
    van Heemst, Diana
    van Oort, Floor V A
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Waldenberger, Melanie
    Wennauer, Roman
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Bergmann, Sven
    Biffar, Reiner
    Blangero, John
    Boomsma, Dorret I
    Bornstein, Stefan R
    Bovet, Pascal
    Brambilla, Paolo
    Brown, Morris J
    Campbell, Harry
    Caulfield, Mark J
    Chakravarti, Aravinda
    Collins, Rory
    Collins, Francis S
    Crawford, Dana C
    Cupples, L Adrienne
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Golay, Alain
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Haas, David W
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Heath, Andrew C
    Hengstenberg, Christian
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Hovingh, G Kees
    Humphries, Steve E
    Hunt, Steven C
    Hypponen, Elina
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jousilahti, Pekka
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Kayser, Manfred
    Kee, Frank
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Kooner, Jaspal S
    Kooperberg, Charles
    Koskinen, Seppo
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lupoli, Sara
    Madden, Pamela A F
    Männistö, Satu
    Manunta, Paolo
    Marette, André
    Matise, Tara C
    McKnight, Barbara
    Meitinger, Thomas
    Moll, Frans L
    Montgomery, Grant W
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Ouwehand, Willem H
    Pasterkamp, Gerard
    Peters, Annette
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ritchie, Marylyn
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schwarz, Peter E H
    Sebert, Sylvain
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Steinthorsdottir, Valgerdur
    Stolk, Ronald P
    Tardif, Jean-Claude
    Tönjes, Anke
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden.
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hayes, M Geoffrey
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Jukema, J Wouter
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Moebus, Susanne
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Powell, Joseph E
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Reinmaa, Eva
    Ridker, Paul M
    Rivadeneira, Fernando
    Rotter, Jerome I
    Saaristo, Timo E
    Saleheen, Danish
    Schlessinger, David
    Slagboom, P Eline
    Snieder, Harold
    Spector, Tim D
    Strauch, Konstantin
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van der Harst, Pim
    Völzke, Henry
    Walker, Mark
    Wareham, Nicholas J
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Deloukas, Panos
    Heid, Iris M
    Lindgren, Cecilia M
    Mohlke, Karen L
    Speliotes, Elizabeth K
    Thorsteinsdottir, Unnur
    Barroso, Inês
    Fox, Caroline S
    North, Kari E
    Strachan, David P
    Beckmann, Jacques S
    Berndt, Sonja I
    Boehnke, Michael
    Borecki, Ingrid B
    McCarthy, Mark I
    Metspalu, Andres
    Stefansson, Kari
    Uitterlinden, André G
    van Duijn, Cornelia M
    Franke, Lude
    Willer, Cristen J
    Price, Alkes L
    Lettre, Guillaume
    Loos, Ruth J F
    Weedon, Michael N
    Ingelsson, Erik
    O'Connell, Jeffrey R
    Abecasis, Goncalo R
    Chasman, Daniel I
    Goddard, Michael E
    Visscher, Peter M
    Hirschhorn, Joel N
    Frayling, Timothy M
    Defining the role of common variation in the genomic and biological architecture of adult human height.2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 11, 1173-86 p.Article in journal (Refereed)
    Abstract [en]

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

1 - 24 of 24
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