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

dc.contributor.authorWen, Wanqing
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorZheng, Wei
dc.date.accessioned2019-10-09T17:41:41Z
dc.date.available2019-10-09T17:41:41Z
dc.date.issued2019-06
dc.identifier.citationPaul 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 V Smith, 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 V R Horimoto, 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, M Abdullah Said, Robert A Scott, Tamar Sofer, Alena Stančáková, Fumihiko Takeuchi, Bamidele O Tayo, Peter J van der Most, Tibor V Varga, 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, H 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, C Charles Gu, Tamara B Harris, Sami Heikkinen, Chew-Kiat Heng, Makoto Hirata, James E Hixson, Barbara V Howard, M 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 Mägi, 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, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), 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, E Shyong Tai, Tien Yin Wong, Jingmin Liu, Jerome I Rotter, W James Gauderman, Michael A Province, Patricia B Munroe, Kenneth Rice, Daniel I Chasman, L Adrienne Cupples, Dabeeru C Rao, Alanna C Morrison, Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions, American Journal of Epidemiology, Volume 188, Issue 6, June 2019, Pages 1033–1054, https://doi.org/10.1093/aje/kwz005en_US
dc.identifier.issn0002-9262
dc.identifier.urihttp://hdl.handle.net/1803/9579
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://academic.oup.com/aje/article/188/6/1033/5304469en_US
dc.description.abstractA 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.en_US
dc.description.sponsorshipWe declare no competing financial interests, except for the following. B.M.P. serves on the Data and Safety Monitoring Board of a clinical trial funded by the manufacturer (Zoll Lifecor Corporation, Pittsburgh, Pennsylvania) and on the Steering Committee of the Yale Open Data Access Project, funded by Johnson & Johnson (New Brunswick, New Jersey). O.H.F. received grants from Metagenics, Inc. (Aliso Viejo, California) on women's health and epigenetics and from Nestle S. A. (Vevey, Switzerland) on child health. M.A.N.'s participation was supported by a consulting contract between Data Tecnica International (Glen Echo, Maryland) and the NIA (Bethesda, Maryland). M.A.N. also consults for Illumina Inc. (San Diego, California), the Michael J. Fox Foundation for Parkinson's Research (New York, New York), and UC Health (Oakland, California), among other organizations. N.P. has received financial support and consultancy fees from several pharmaceutical companies that manufacture either blood pressure-lowering or lipid-lowering agents or both (Sanofi (Guildford, United Kingdom), Amgen (Uxbridge, United Kingdom), Takeda (London, United Kingdom), Servier (Suresnes, France), and Pfizer (Tadwork, United Kingdom)) but holds no stock or shares in any such companies. P. S. has received research awards from Pfizer Inc. (New York, New York). J.B.J. serves as a consultant for the Mundipharma Company (Cambridge, United Kingdom), is a patent holder with Biocompatibles UK Ltd. (Franham, United Kingdom) (patent no. 20120263794; "Treatment of Eye Diseases Using Encapsulated Cells Encoding and Secreting Neuroprotective Factor and/or Anti-Angiogenic Factor"), and is a patent applicant with the University of Heidelberg (Heidelberg, Germany) (Europaische Patentanmeldung no. 15 000 771.4; " Agents for Use in the Therapeutic or Prophylactic Treatment of Myopia or Hyperopia").en_US
dc.language.isoen_USen_US
dc.publisherAMERICAN JOURNAL OF EPIDEMIOLOGYen_US
dc.rightsThis work is written by (a) US Government employee(s) and is in the public domain in the US.
dc.source.urihttps://academic.oup.com/aje/article/188/6/1033/5304469
dc.subjectalcohol consumptionen_US
dc.subjectcholesterolen_US
dc.subjectgene-environment ineractionsen_US
dc.subjectgene-lifestyle interactionsen_US
dc.subjectgenome-wide association studiesen_US
dc.subjectlipidsen_US
dc.subjecttriglyceridesen_US
dc.subjectdensity-lipoprotein cholesterolen_US
dc.subjectcoronary-heart-diseaseen_US
dc.subjectHDL cholesterolen_US
dc.subjectlow-frequencyen_US
dc.subjectblood-lipidsen_US
dc.subjectmetaanalysisen_US
dc.subjectplasmaen_US
dc.subjectconsumptionen_US
dc.subjectindividualsen_US
dc.subjectVEGFBen_US
dc.subject.lcshcholesterolen_US
dc.subject.lcshDrinking of alcoholic beveragesen_US
dc.subject.lcshCoronary heart diseaseen_US
dc.titleMultiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactionsen_US
dc.typeArticleen_US
dc.identifier.doi10.1093/aje/kwz005


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