Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
- 2019
Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1996 - 2006
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 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 Stage 1 and Stage 2, 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
English
0002-9262
10.1093/aje/kwz005 [doi] 5304469 [pii]
*Alcohol Drinking/ep [Epidemiology] *Lipids/bl [Blood] Adolescent Adult Aged Cholesterol, HDL/bl [Blood] Cholesterol, LDL/bl [Blood] Continental Population Groups Female Genome-Wide Association Study Genotype Humans Life Style Male Middle Aged Phenotype Triglycerides/bl [Blood] Vascular Endothelial Growth Factor B Young Adult