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

Publication Abstract

de Vries, Paul S., Jennifer A. Smith, Sharon L. R. Kardia, David Weir, Erin Bakshis Ware, Jessica Faul, Zheng Wang, Michael R. Brown, et al. Forthcoming. "Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions." American Journal of Epidemiology.

An individual'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 multi-ancestry 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 five ancestry groups. Genetic main and interaction effects were jointly assessed by 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 Stage 1 and Stage 2, 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.

10.1093/aje/kwz005

Browse | Search | Next

PSC In The News

RSS Feed icon

Barbara Anderson comments in NYT on Federal Law that protects citienship status data from distribution by the Census Bureau. @UM_PSC

Anderson discusses impact of Administration's ongoing pursuit of Citizenship information around the 2020 Census with Michigan Radio

Burgard correlates job insecurity higher with negative overall health and depression than the impact of job loss and regain

More News

Highlights

Colter Mitchell receives Presidential Early Career Award for Scientists and Engineers (PECASE)

Frey receives 2019 ASA Distinguished Contributions to Teaching Award

More Highlights


Connect with PSC follow PSC on Twitter Like PSC on Facebook