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

Paul de Vries 1 Michael Brown 1 Amy Bentley 2 Yun Sung 1, 3 Thomas Winkler 4 Ioanna Ntalla 5 Karen Schwander 6 Aldi Kraja 3 Xiuqing Guo 7 Nora Franceschini 8 Ching-Yu Cheng 9, 10 Xueling Sim 10 Dina Vojinovic 11 Jennifer Huffman Solomon Musani Changwei Li Mary Feitosa 3 Melissa Richard Raymond Noordam Hugues Aschard 12 Traci Bartz Lawrence Bielak Xuan Deng Rajkumar Dorajoo Kurt Lohman Alisa Manning Tuomo Rankinen Albert Smith Salman Tajuddin Evangelos Evangelou Mariaelisa Graff 8 Maris Alver Mathilde Boissel 13 Jin Fang Chai 10 Xu Chen Jasmin Divers Ilaria Gandin Chuan Gao Anuj Goel Yanick Hagemeijer Sarah Harris Fernando Hartwig Meian He Andrea Horimoto Fang-Chi Hsu Anne Jackson Anuradhani Kasturiratne Pirjo Komulainen Brigitte Kühnel Federica Laguzzi Joseph Lee Jian'An Luan Leo-Pekka Lyytikäinen Nana Matoba Ilja Nolte Maik Pietzner Muhammad Riaz M Abdullah Said Robert Scott Tamar Sofer Alena Stančáková Fumihiko Takeuchi Bamidele Tayo Peter van der Most Tibor Varga Yajuan Wang 8 Erin Ware Wanqing Wen Lisa Yanek Weihua Zhang Jing Hua Zhao Saima Afaq Najaf Amin 11 Marzyeh Amini Dan Arking Tin Aung 9 Christie Ballantyne Eric Boerwinkle Ulrich Broeckel Archie Campbell Mickaël Canouil 13 Sabanayagam Charumathi 9 Yii-Der Ida Chen 7 John Connell Ulf de Faire Lisa de las Fuentes 3 Renée de Mutsert H Janaka de Silva Jingzhong Ding Anna Dominiczak Qing Duan Charles Eaton Ruben Eppinga Jessica Faul Virginia Fisher Terrence Forrester Oscar Franco 11 Yechiel Friedlander Mohsen Ghanbari 11 Franco Giulianini Hans Grabe Megan Grove 1 C Charles Gu 3 Tamara Harris Sami Heikkinen Chew-Kiat Heng Makoto Hirata James Hixson Barbara Howard M Arfan Ikram 11 David Jacobs Craig Johnson Jost Bruno Jonas Candace Kammerer Tomohiro Katsuya Chiea Chuen Khor Tuomas Kilpeläinen Woon-Puay Koh 10 Heikki Koistinen Ivana Kolcic Charles Kooperberg Jose Krieger Steve Kritchevsky Michiaki Kubo Johanna Kuusisto Timo Lakka Carl Langefeld Claudia Langenberg Lenore Launer Benjamin Lehne Rozenn Lemaitre Yize Li 3 Jingjing Liang Jianjun Liu Kiang Liu Marie Loh Tin Louie Reedik Mägi Ani Manichaikul Colin Mckenzie Thomas Meitinger Andres Metspalu Yuri Milaneschi Lili Milani Karen Mohlke Thomas Mosley Kenneth Mukamal Mike Nalls Matthias Nauck Christopher Nelson Nona Sotoodehnia Jeff O'Connell Nicholette Palmer Raha Pazoki Nancy Pedersen Annette Peters Patricia Peyser Ozren Polasek Neil Poulter Leslie Raffel Olli Raitakari Alex Reiner Treva Rice 3 Stephen Rich Antonietta Robino Jennifer Robinson Lynda Rose Igor Rudan Carsten Schmidt Pamela Schreiner William Scott Peter Sever Yuan Shi 9 Stephen Sidney Mario Sims Blair Smith Jennifer Smith Harold Snieder John Starr Konstantin Strauch Nicholas Tan 9 Kent Taylor 7 Yik Ying Teo 10 Yih Chung Tham 9 André Uitterlinden 11 Diana van Heemst Dragana Vuckovic Melanie Waldenberger Lihua Wang 3 Yujie Wang Zhe Wang 1 Wen Bin Wei Christine Williams 3 Gregory Wilson Mary Wojczynski 3 Jie Yao 7 Bing Yu Caizheng Yu Jian-Min Yuan Wei Zhao Alan Zonderman Diane Becker Michael Boehnke Donald Bowden John Chambers Ian Deary Tõnu Esko Martin Farrall Paul Franks Barry Freedman Philippe Froguel 13 Paolo Gasparini Christian Gieger Bernardo Horta Yoichiro Kamatani Norihiro Kato Jaspal Kooner Markku Laakso Karin Leander Terho Lehtimäki Patrik Magnusson Brenda Penninx Alexandre Pereira Rainer Rauramaa Nilesh Samani James Scott Xiao-Ou Shu Pim van der Harst Lynne Wagenknecht Ya Xing Wang Nicholas Wareham Hugh Watkins David Weir Ananda Wickremasinghe Wei Zheng Paul Elliott Kari North 8 Claude Bouchard Michele Evans Vilmundur Gudnason Ching-Ti Liu Yongmei Liu Bruce Psaty Paul Ridker Rob van Dam 10 Sharon Kardia Xiaofeng Zhu Charles Rotimi 2 Dennis Mook-Kanamori Myriam Fornage 1 Tanika Kelly Ervin Fox Caroline Hayward Cornelia van Duijn 11 E Shyong Tai 10 Tien Yin Wong 9 Jingmin Liu Jerome Rotter 7 W James Gauderman Michael Province 3 Patricia Munroe 5 Kenneth Rice Daniel Chasman L Adrienne Cupples Dabeeru Rao 3 Alanna Morrison 1
1 UTHealth - The University of Texas Health Science Center at Houston
2 NIH - National Institutes of Health [Bethesda]
3 Washington University in St Louis
4 University of Regensburg
5 QMUL - Queen Mary University of London
6 Washington University School of Medicine in St. Louis
7 Harbor UCLA Medical Center [Torrance, Ca.]
8 UNC - University of North Carolina at Chapel Hill
9 Singapore National Eye Centre and Duke-NUS [Singapore]
10 NUS - National University of Singapore
11 Erasmus MC - Erasmus University Medical Center [Rotterdam]
12 Département de Biologie Computationnelle - Department of Computational Biology
13 Institut Pasteur de Lille
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.
Keywords : alcohol consumption cholesterol gene-environment interactions gene-lifestyle interactions genome-wide association studies lipids triglycerides
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Submitted on : Monday, July 5, 2021 - 4:50:26 PM
Last modification on : Tuesday, October 19, 2021 - 10:29:31 PM

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Paul de Vries, Michael Brown, Amy Bentley, Yun Sung, Thomas Winkler, et al.. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. American Journal of Epidemiology, Oxford University Press (OUP), 2019, 188 (6), pp.1033-1054. ⟨10.1093/aje/kwz005⟩. ⟨pasteur-03278557⟩

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