| Literature DB >> 30698716 |
Paul S de Vries1, Michael R Brown1, Amy R Bentley2, Yun J Sung3, Thomas W Winkler4, Ioanna Ntalla5, Karen Schwander3, Aldi T Kraja6, Xiuqing Guo7, Nora Franceschini8, Ching-Yu Cheng9,10,11, Xueling Sim12, Dina Vojinovic13, Jennifer E Huffman14, Solomon K Musani15, Changwei Li16, Mary F Feitosa6, Melissa A Richard17, Raymond Noordam18, Hugues Aschard19,20, Traci M Bartz21, Lawrence F Bielak22, Xuan Deng23, Rajkumar Dorajoo24, Kurt K Lohman25, Alisa K Manning26,27, Tuomo Rankinen28, Albert V Smith29,30, Salman M Tajuddin31, Evangelos Evangelou32,33, Mariaelisa Graff8, Maris Alver34, Mathilde Boissel35, Jin Fang Chai12, Xu Chen36, Jasmin Divers37, Ilaria Gandin38, Chuan Gao39, Anuj Goel40,41, Yanick Hagemeijer42, Sarah E Harris43,44, Fernando P Hartwig45,46, Meian He47, Andrea R V R Horimoto48, Fang-Chi Hsu37, Anne U Jackson49, Anuradhani Kasturiratne50, Pirjo Komulainen51, Brigitte Kühnel52,53, Federica Laguzzi54, Joseph H Lee55, Jian'an Luan56, Leo-Pekka Lyytikäinen57,58, Nana Matoba59, Ilja M Nolte60, Maik Pietzner61,62, Muhammad Riaz63,64, M Abdullah Said42, Robert A Scott56, Tamar Sofer27,65, Alena Stančáková66, Fumihiko Takeuchi67, Bamidele O Tayo68, Peter J van der Most60, Tibor V Varga69, Yajuan Wang70, Erin B Ware71, Wanqing Wen72, Lisa R Yanek73, Weihua Zhang32,74, Jing Hua Zhao56, Saima Afaq32, Najaf Amin13, Marzyeh Amini60, Dan E Arking75, Tin Aung9,11,76, Christie Ballantyne77,78, Eric Boerwinkle79,80, Ulrich Broeckel81, Archie Campbell82, Mickaël Canouil35, Sabanayagam Charumathi9,10, Yii-Der Ida Chen7, John M Connell83, Ulf de Faire54, Lisa de Las Fuentes3,84, Renée de Mutsert85, H Janaka de Silva86, Jingzhong Ding87, Anna F Dominiczak88, Qing Duan89, Charles B Eaton90, Ruben N Eppinga42, Jessica D Faul71, Virginia Fisher23, Terrence Forrester91, Oscar H Franco13,92, Yechiel Friedlander93, Mohsen Ghanbari13,94, Franco Giulianini, Hans J Grabe95, Megan L Grove1, C Charles Gu3, Tamara B Harris96, Sami Heikkinen66,97, Chew-Kiat Heng98,99, Makoto Hirata100, James E Hixson79, Barbara V Howard101,102, M Arfan Ikram13,103,104, David R Jacobs105, Craig Johnson106, Jost Bruno Jonas107,108, Candace M Kammerer109, Tomohiro Katsuya110,111, Chiea Chuen Khor24,112, Tuomas O Kilpeläinen113,114, Woon-Puay Koh12,115, Heikki A Koistinen116,117,118, Ivana Kolcic, Charles Kooperberg119, Jose E Krieger48, Steve B Kritchevsky120, Michiaki Kubo121, Johanna Kuusisto66, Timo A Lakka51,97,122, Carl D Langefeld37, Claudia Langenberg56, Lenore J Launer96, Benjamin Lehne32, Rozenn N Lemaitre123, Yize Li3, Jingjing Liang70, Jianjun Liu24,124, Kiang Liu125, Marie Loh32,126, Tin Louie127, Reedik Mägi34, Ani W Manichaikul128, Colin A McKenzie91, Thomas Meitinger129,130, Andres Metspalu34, Yuri Milaneschi131, Lili Milani34, Karen L Mohlke89, Thomas H Mosley132, Kenneth J Mukamal133, Mike A Nalls134,135, Matthias Nauck61,62, Christopher P Nelson63,64, Nona Sotoodehnia136, Jeff R O'Connell137,138, Nicholette D Palmer139, Raha Pazoki32, Nancy L Pedersen36, Annette Peters53,62, Patricia A Peyser22, Ozren Polasek140,141,142, Neil Poulter143, Leslie J Raffel144, Olli T Raitakari145,146, Alex P Reiner119, Treva K Rice3, Stephen S Rich147, Antonietta Robino148, Jennifer G Robinson149, Lynda M Rose150, Igor Rudan151, Carsten O Schmidt152, Pamela J Schreiner105, William R Scott32,153, Peter Sever153, Yuan Shi9, Stephen Sidney154, Mario Sims15, Blair H Smith155, Jennifer A Smith22,71, Harold Snieder60, John M Starr43,156, Konstantin Strauch157,158, Nicholas Tan9,11, Kent D Taylor7, Yik Ying Teo12,24,159,160,161, Yih Chung Tham9, André G Uitterlinden13,162, Diana van Heemst18, Dragana Vuckovic38, Melanie Waldenberger52,53, Lihua Wang6, Yujie Wang8, Zhe Wang1, Wen Bin Wei163, Christine Williams6, Gregory Wilson164, Mary K Wojczynski6, Jie Yao7, Bing Yu1, Caizheng Yu47, Jian-Min Yuan165,166, Wei Zhao22, Alan B Zonderman167, Diane M Becker73, Michael Boehnke49, Donald W Bowden139, John C Chambers32,74,168,169,170,171, Ian J Deary43,172, Tõnu Esko34,173, Martin Farrall40,41, Paul W Franks69,174,175,176, Barry I Freedman177, Philippe Froguel35,178, Paolo Gasparini38,148, Christian Gieger52,179, Bernardo L Horta45, Yoichiro Kamatani59, Norihiro Kato67, Jaspal S Kooner74,153,169,171, Markku Laakso66, Karin Leander54, Terho Lehtimäki57,58, Patrik K E Magnusson36, Brenda Penninx131, Alexandre C Pereira48, Rainer Rauramaa51, Nilesh J Samani63,64, James Scott153, Xiao-Ou Shu72, Pim van der Harst42,180, Lynne E Wagenknecht181, Ya Xing Wang182, Nicholas J Wareham56, Hugh Watkins40,41, David R Weir71, Ananda R Wickremasinghe50, Wei Zheng72, Paul Elliott32,170,171,183,184, Kari E North8,185, Claude Bouchard28, Michele K Evans31, Vilmundur Gudnason29,30, Ching-Ti Liu23, Yongmei Liu186, Bruce M Psaty187,188, Paul M Ridker150,189, Rob M van Dam12,174,124, Sharon L R Kardia22, Xiaofeng Zhu70, Charles N Rotimi2, Dennis O Mook-Kanamori85,190, Myriam Fornage1,17, Tanika N Kelly191, Ervin R Fox192, Caroline Hayward14, Cornelia M van Duijn13, E Shyong Tai12,115,124, Tien Yin Wong9,11,76, Jingmin Liu193, Jerome I Rotter7, W James Gauderman194, Michael A Province6, Patricia B Munroe5,195, Kenneth Rice127, Daniel I Chasman150,189, L Adrienne Cupples23,196, Dabeeru C Rao3, Alanna C Morrison1.
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. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.Entities:
Keywords: alcohol consumption; cholesterol; gene-environment interactions; gene-lifestyle interactions; genome-wide association studies; lipids; triglycerides
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Year: 2019 PMID： 30698716 PMCID： PMC6545280 DOI： 10.1093/aje/kwz005
Source DB: PubMed Journal: Am J Epidemiol ISSN： 0002-9262 Impact factor: 5.363