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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

Citation
de Vries, P. S., et al. “Multiancestry Genome-Wide Association Study Of Lipid Levels Incorporating Gene-Alcohol Interactions.”. American Journal Of Epidemiology, pp. 1033-1054.
Center University of Michigan UCSD-UCLA
Multicenter
Multicenter
Author Paul S de Vries, Michael R Brown, Amy R Bentley, Yun J Sung, Thomas W Winkler, Ioanna Ntalla, Karen Schwander, Aldi T Kraja, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jennifer E Huffman, Solomon K Musani, Changwei Li, Mary F Feitosa, Melissa A Richard, Raymond Noordam, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Xuan Deng, Rajkumar Dorajoo, Kurt K Lohman, Alisa K Manning, Tuomo Rankinen, Albert Smith V, Salman M Tajuddin, Evangelos Evangelou, Mariaelisa Graff, Maris Alver, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Ilaria Gandin, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E Harris, Fernando P Hartwig, Meian He, Andrea R R Horimoto V, Fang-Chi Hsu, Anne U Jackson, Anuradhani Kasturiratne, Pirjo Komulainen, Brigitte Kühnel, Federica Laguzzi, Joseph H Lee, Jian'an Luan, Leo-Pekka Lyytikäinen, Nana Matoba, Ilja M Nolte, Maik Pietzner, Muhammad Riaz, Abdullah Said, Robert A Scott, Tamar Sofer, Alena Stancáková, Fumihiko Takeuchi, Bamidele O Tayo, Peter J van der Most, Tibor Varga V, Yajuan Wang, Erin B Ware, Wanqing Wen, Lisa R Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Najaf Amin, Marzyeh Amini, Dan E Arking, Tin Aung, Christie Ballantyne, Eric Boerwinkle, Ulrich Broeckel, Archie Campbell, Mickaël Canouil, Sabanayagam Charumathi, Yii-Der Ida Chen, John M Connell, Ulf de Faire, Lisa de Las Fuentes, Renée de Mutsert, Janaka de Silva, Jingzhong Ding, Anna F Dominiczak, Qing Duan, Charles B Eaton, Ruben N Eppinga, Jessica D Faul, Virginia Fisher, Terrence Forrester, Oscar H Franco, Yechiel Friedlander, Mohsen Ghanbari, Franco Giulianini, Hans J Grabe, Megan L Grove, Charles Gu, Tamara B Harris, Sami Heikkinen, Chew-Kiat Heng, Makoto Hirata, James E Hixson, Barbara Howard V, Arfan Ikram, InterAct Consortium, David R Jacobs, Craig Johnson, Jost Bruno Jonas, Candace M Kammerer, Tomohiro Katsuya, Chiea Chuen Khor, Tuomas O Kilpeläinen, Woon-Puay Koh, Heikki A Koistinen, Ivana Kolcic, Charles Kooperberg, Jose E Krieger, Steve B Kritchevsky, Michiaki Kubo, Johanna Kuusisto, Timo A Lakka, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Benjamin Lehne, Rozenn N Lemaitre, Yize Li, Jingjing Liang, Jianjun Liu, Kiang Liu, Marie Loh, Tin Louie, Reedik Magi, Ani W Manichaikul, Colin A McKenzie, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Lili Milani, Karen L Mohlke, Thomas H Mosley, Kenneth J Mukamal, Mike A Nalls, Matthias Nauck, Christopher P Nelson, Nona Sotoodehnia, Jeff R O'Connell, Nicholette D Palmer, Raha Pazoki, Nancy L Pedersen, Annette Peters, Patricia A Peyser, Ozren Polasek, Neil Poulter, Leslie J Raffel, Olli T Raitakari, Alex P Reiner, Treva K Rice, Stephen S Rich, Antonietta Robino, Jennifer G Robinson, Lynda M Rose, Igor Rudan, Carsten O Schmidt, Pamela J Schreiner, William R Scott, Peter Sever, Yuan Shi, Stephen Sidney, Mario Sims, Blair H Smith, Jennifer A Smith, Harold Snieder, John M Starr, Konstantin Strauch, Nicholas Tan, Kent D Taylor, Yik Ying Teo, Yih Chung Tham, André G Uitterlinden, Diana van Heemst, Dragana Vuckovic, Melanie Waldenberger, Lihua Wang, Yujie Wang, Zhe Wang, Wen Bin Wei, Christine Williams, Gregory Wilson, Mary K Wojczynski, Jie Yao, Bing Yu, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Alan B Zonderman, Diane M Becker, Michael Boehnke, Donald W Bowden, John C Chambers, Ian J Deary, Tõnu Esko, Martin Farrall, Paul W Franks, Barry I Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Bernardo L Horta, Yoichiro Kamatani, Norihiro Kato, Jaspal S Kooner, Markku Laakso, Karin Leander, Terho Lehtimäki, Groningen The Netherlands Lifelines Cohort, Patrik K E Magnusson, Brenda Penninx, Alexandre C Pereira, Rainer Rauramaa, Nilesh J Samani, James Scott, Xiao-Ou Shu, Pim van der Harst, Lynne E Wagenknecht, Ya Xing Wang, Nicholas J Wareham, Hugh Watkins, David R Weir, Ananda R Wickremasinghe, Wei Zheng, Paul Elliott, Kari E North, Claude Bouchard, Michele K Evans, Vilmundur Gudnason, Ching-Ti Liu, Yongmei Liu, Bruce M Psaty, Paul M Ridker, Rob M van Dam, Sharon L R Kardia, Xiaofeng Zhu, Charles N Rotimi, Dennis O Mook-Kanamori, Myriam Fornage, Tanika N Kelly, Ervin R Fox, Caroline Hayward, Cornelia M van Duijn, Shyong Tai, Tien Yin Wong, Jingmin Liu, Jerome I Rotter, James Gauderman, Michael A Province, Patricia B Munroe, Kenneth Rice, Daniel I Chasman, Adrienne Cupples, Dabeeru C Rao, Alanna C Morrison
Keywords alcohol consumption, cholesterol, gene-environment interactions, gene-lifestyle interactions, genome-wide association studies, lipids, triglycerides
Abstract

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 × 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 × 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.

Year of Publication
2019
Journal
American journal of epidemiology
Volume
188
Issue
6
Number of Pages
1033-1054
Date Published
12/2019
ISSN Number
1476-6256
DOI
10.1093/aje/kwz005
Alternate Journal
Am. J. Epidemiol.
PMID
30698716
PMCID
PMC6545280
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