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

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InterAct Consortium , LifeLines Cohort Study Grp , de Vries , P S , Brown , M R , Bentley , A R , Heikkinen , S , Koistinen , H A & Weir , D R 2019 , ' Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions ' , American Journal of Epidemiology , vol. 188 , no. 6 , pp. 1033-1054 .

Title: Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
Author: InterAct Consortium; LifeLines Cohort Study Grp; de Vries, Paul S.; Brown, Michael R.; Bentley, Amy R.; Heikkinen, Sami; Koistinen, Heikki A.; Weir, David R.
Contributor organization: University Management
Department of Medicine
University of Helsinki
Endokrinologian yksikkö
HUS Abdominal Center
Date: 2019-06
Language: eng
Number of pages: 22
Belongs to series: American Journal of Epidemiology
ISSN: 0002-9262
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 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.
Subject: alcohol consumption
gene-environment interactions
gene-lifestyle interactions
genome-wide association studies
3142 Public health care science, environmental and occupational health
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion

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