2019-06-01
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
Publication
Publication
American Journal of Epidemiology , Volume 188 - Issue 6 p. 1033- 1054
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.
| Additional Metadata | |
|---|---|
| , , , , , , | |
| doi.org/10.1093/aje/kwz005, hdl.handle.net/1765/117281 | |
| American Journal of Epidemiology | |
| , , | |
| Organisation | Department of Epidemiology |
|
de Vries, P., Brown, M. R., Bentley, A., Sung, Y.J. (Yun J.), Winkler, T. W., Ntalla, I., … Morrison, A. (2019). Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. American Journal of Epidemiology, 188(6), 1033–1054. doi:10.1093/aje/kwz005 |
|