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Journal Articles American Journal of Epidemiology Year : 2019

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

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Jennifer Huffman
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Solomon Musani
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Changwei Li
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Archie Campbell
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John Connell
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Ulf de Faire
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Renée de Mutsert
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H Janaka de Silva
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Jingzhong Ding
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Qing Duan
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Charles Eaton
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Jessica Faul
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Claudia Langenberg
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Benjamin Lehne
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Rozenn Lemaitre
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Jingjing Liang
Jianjun Liu
Kiang Liu
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Marie Loh
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Tin Louie
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Ani Manichaikul
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Colin Mckenzie
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Thomas Meitinger
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Andres Metspalu
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Yuri Milaneschi
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Lili Milani
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Karen Mohlke
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Thomas Mosley
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Kenneth Mukamal
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Mike Nalls
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Matthias Nauck
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Christopher Nelson
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Nona Sotoodehnia
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Jeff O'Connell
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Nicholette Palmer
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Raha Pazoki
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Patricia Peyser
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Ozren Polasek
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Leslie Raffel
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Olli Raitakari
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Stephen Rich
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Antonietta Robino
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Lynda Rose
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Igor Rudan
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Carsten Schmidt
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Pamela Schreiner
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William Scott
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Peter Sever
Stephen Sidney
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Mario Sims
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Blair Smith
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Jennifer Smith
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Harold Snieder
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John Starr
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Konstantin Strauch
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Dragana Vuckovic
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Melanie Waldenberger
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Yujie Wang
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Wen Bin Wei
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Gregory Wilson
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Bing Yu
Caizheng Yu
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Jian-Min Yuan
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Wei Zhao
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Alan Zonderman
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Diane Becker
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Michael Boehnke
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Donald Bowden
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John Chambers
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Ian Deary
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Tõnu Esko
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Martin Farrall
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Paul Franks
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Barry Freedman
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Paolo Gasparini
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Christian Gieger
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Bernardo Horta
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Yoichiro Kamatani
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Norihiro Kato
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Jaspal Kooner
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Markku Laakso
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Karin Leander
Terho Lehtimäki
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Patrik Magnusson
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Brenda Penninx
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Alexandre Pereira
Rainer Rauramaa
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Nilesh Samani
James Scott
Xiao-Ou Shu
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Pim van Der Harst
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Lynne Wagenknecht
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Ya Xing Wang
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Nicholas Wareham
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Hugh Watkins
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David Weir
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Ananda Wickremasinghe
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Wei Zheng
Paul Elliott
Claude Bouchard
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Vilmundur Gudnason
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Ching-Ti Liu
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Yongmei Liu
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Paul Ridker
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Xiaofeng Zhu
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Dennis Mook-Kanamori
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Tanika Kelly
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Ervin Fox
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Caroline Hayward
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Jingmin Liu
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Kenneth Rice
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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.

Dates and versions

pasteur-03278557 , version 1 (05-07-2021)

Identifiers

Cite

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, 2019, 188 (6), pp.1033-1054. ⟨10.1093/aje/kwz005⟩. ⟨pasteur-03278557⟩

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