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  • 1. de Vries, Paul S.
    et al.
    Brown, Michael R.
    Bentley, Amy R.
    Sung, Yun J.
    Winkler, Thomas W.
    Ntalla, Ioanna
    Schwander, Karen
    Kraja, Aldi T.
    Guo, Xiuqing
    Franceschini, Nora
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Huffman, Jennifer E.
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Richard, Melissa A.
    Noordam, Raymond
    Aschard, Hugues
    Bartz, Traci M.
    Bielak, Lawrence F.
    Deng, Xuan
    Dorajoo, Rajkumar
    Lohman, Kurt K.
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert V.
    Tajuddin, Salman M.
    Evangelou, Evangelos
    Graff, Mariaelisa
    Alver, Maris
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gandin, Ilaria
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    Hartwig, Fernando P.
    He, Meian
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuehnel, Brigitte
    Laguzzi, Federica
    Lee, Joseph H.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Matoba, Nana
    Nolte, Ilja M.
    Pietzner, Maik
    Riaz, Muhammad
    Said, M. Abdullah
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Yajuan
    Ware, Erin B.
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Aung, Tin
    Ballantyne, Christie
    Boerwinkle, Eric
    Broeckel, Ulrich
    Campbell, Archie
    Canouil, Mickael
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Connell, John M.
    de Faire, Ulf
    de las Fuentes, Lisa
    de Mutsert, Renee
    de Silva, H. Janaka
    Ding, Jingzhong
    Dominiczak, Anna F.
    Duan, Qing
    Eaton, Charles B.
    Eppinga, Ruben N.
    Faul, Jessica D.
    Fisher, Virginia
    Forrester, Terrence
    Franco, Oscar H.
    Friedlander, Yechiel
    Ghanbari, Mohsen
    Giulianini, Franco
    Grabe, Hans J.
    Grove, Megan L.
    Gu, C. Charles
    Harris, Tamara B.
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hixson, James E.
    Howard, Barbara V.
    Ikram, M. Arfan
    Jacobs, David R., Jr.
    Johnson, Craig
    Jonas, Jost Bruno
    Kammerer, Candace M.
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Koistinen, Heikki A.
    Kolcic, Ivana
    Kooperberg, Charles
    Krieger, Jose E.
    Kritchevsky, Steve B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lemaitre, Rozenn N.
    Li, Yize
    Liang, Jingjing
    Liu, Jianjun
    Liu, Kiang
    Loh, Marie
    Louie, Tin
    Magi, Reedik
    Manichaikul, Ani W.
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Mosley, Thomas H., Jr.
    Mukamal, Kenneth J.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    Sotoodehnia, Nona
    O'Connell, Jeff R.
    Palmer, Nicholette D.
    Pazoki, Raha
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Poulter, Neil
    Raffel, Leslie J.
    Raitakari, Olli T.
    Reiner, Alex P.
    Rice, Treva K.
    Rich, Stephen S.
    Robino, Antonietta
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rudan, Igor
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Sever, Peter
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Smith, Blair H.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Tan, Nicholas
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Uitterlinden, Andre G.
    van Heemst, Diana
    Vuckovic, Dragana
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Yujie
    Wang, Zhe
    Wei, Wen Bin
    Williams, Christine
    Wilson, Gregory, Sr.
    Wojczynski, Mary K.
    Yao, Jie
    Yu, Bing
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Nutrition, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo L.
    Kamatani, Yoichiro
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Leander, Karin
    Lehtimaki, Terho
    Magnusson, Patrik K. E.
    Penninx, Brenda
    Pereira, Alexandre C.
    Rauramaa, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wang, Ya Xing
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Zheng, Wei
    Elliott, Paul
    North, Kari E.
    Bouchard, Claude
    Evans, Michele K.
    Gudnason, Vilmundur
    Liu, Ching-Ti
    Liu, Yongmei
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Kardia, Sharon L. R.
    Zhu, Xiaofeng
    Rotimi, Charles N.
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Liu, Jingmin
    Rotter, Jerome I.
    Gauderman, W. James
    Province, Michael A.
    Munroe, Patricia B.
    Rice, Kenneth
    Chasman, Daniel I.
    Cupples, L. Adrienne
    Rao, Dabeeru C.
    Morrison, Alanna C.
    Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions2019In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, no 6, p. 1033-1054Article in journal (Refereed)
    Abstract [en]

    A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

  • 2. Justice, Anne E.
    et al.
    Karaderi, Tugce
    Highland, Heather M.
    Young, Kristin L.
    Graff, Mariaelisa
    Lu, Yingchang
    Turcot, Valerie
    Auer, Paul L.
    Fine, Rebecca S.
    Guo, Xiuqing
    Schurmann, Claudia
    Lempradl, Adelheid
    Marouli, Eirini
    Mahajan, Anubha
    Winkler, Thomas W.
    Locke, Adam E.
    Medina-Gomez, Carolina
    Esko, Tonu
    Vedantam, Sailaja
    Giri, Ayush
    Lo, Ken Sin
    Alfred, Tamuno
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Heard-Costa, Nancy L.
    Feitosa, Mary F.
    Manning, Alisa K.
    Willems, Sara M.
    Sivapalaratnam, Suthesh
    Abecasis, Goncalo
    Alam, Dewan S.
    Allison, Matthew
    Amouyel, Philippe
    Arzumanyanm, Zorayr
    Balkau, Beverley
    Bastarache, Lisa
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Broer, Linda
    Burt, Amber A.
    Butterworth, Adam S.
    Caulfield, Markj
    Cesana, Giancarlo
    Chambers, John C.
    Chasman, Daniel, I
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audreyy
    Collins, Francis S.
    Cook, James P.
    Cox, Amanda J.
    Crosslin, David S.
    Danesh, John
    de Bakker, Paul I. W.
    de Denus, Simon
    de Mutsert, Renee
    Dedoussis, George
    Demerath, Ellen W.
    Dennis, Joe G.
    Denny, Josh C.
    Di Angelantonio, Emanuele
    Doerr, Marcus
    Drenos, Fotios
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Fornage, Myriam
    Fox, Caroline S.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Giedraitis, Vilmantas
    Girotto, Giorgia
    Gorski, Mathias
    Grallert, Harald
    Grarup, Niels
    Groves, Megan L.
    Gustafsson, Stefan
    Haessler, Jeff
    Hansen, Torben
    Hattersley, Andrew T.
    Hayward, Caroline
    Heid, Iris M.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Hung, Yi-Jen
    Hveem, Kristian
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jarvik, Gail P.
    Jia, Yucheng
    Jorgensen, Torben
    Jousilahti, Pekka
    Justesen, Johanne M.
    Kahali, Bratati
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kee, Frank
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kovacs, Peter
    Kraemer, Bernhard K.
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    La Nge, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lee, Wen-Jane
    Lehtimaeki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    RuifangLi-Gao,
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstroem, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    MacGregor, Stuart
    Magi, Reedik
    Mannisto, Satu
    Marenne, Gaelle
    Marten, Jonathan
    Mascal, Nicholas G. D.
    McCarthy, Mark, I
    Meidtner, Karina
    Mihailov, Evelin
    Moilanen, Leena
    Moitry, Marie
    Mook-Kanamori, Dennis O.
    Morgan, Anna
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Ntalla, Ioanna
    Owen, Katharine R.
    Pedersen, Oluf
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    James, A.
    Perry, John R. B.
    Pers, Tune H.
    Ewing, Ailith
    Polasek, Ozren
    Rasheed, Asif
    Raulerson, Chelsea K.
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Ridker, Paul M.
    Rivas, Manuel A.
    Robertson, Neil R.
    Robino, Antonietta
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Blair H.
    Smith, Jennifer A.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swart, Karin M. A.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Torres, Mina
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vanhala, Mauno
    Varma, Rohit
    Vermeulen, Sita H.
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wareham, N. Icholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Verges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zheng, He
    Zhou, Wei
    Zillikens, M. Carola
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Pospisilik, J. Andrew
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    Mohlke, Karen L.
    Rotter, Jerome, I
    Kutalik, Zoltan
    Hirschhorn, Joel N.
    Cupples, L. Adrienne
    Loos, Ruth J. F.
    North, Kari E.
    Lindgren, Cecilia M.
    O'Connell, Jeffrey R.
    Raitakari, Olli T.
    Lange, Leslie A.
    Uitterlinden, Andr G.
    Grove, Megan L.
    Masca, Nicholas G. D.
    Luan, Jianan
    Wareham, Nicholas J.
    Esko, Tnu
    De Bakker, Paul Iw
    Caulfield, Mark J.
    Mller-Nurasyid, Martina
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 452-469Article in journal (Refereed)
    Abstract [en]

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

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