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

de Vries, Paul S ; V. Varga, Tibor LU ; Franks, Paul LU and Morrison, Alanna C (2019) In American Journal of Epidemiology 188(6). p.1033-1054
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... (More)
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. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019. (Less)
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author
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alcohol consumption, cholesterol, gene-environment interactions, gene-lifestyle interactions, genome-wide association studies, lipids, triglycerides
in
American Journal of Epidemiology
volume
188
issue
6
pages
22 pages
publisher
Oxford University Press
external identifiers
  • scopus:85067087923
  • pmid:30698716
ISSN
0002-9262
DOI
10.1093/aje/kwz005
language
English
LU publication?
yes
additional info
Export Date: 1 July 2019
id
214a185e-d344-42e1-8185-4c5840429109
date added to LUP
2019-07-01 10:50:37
date last changed
2020-01-22 07:42:28
@article{214a185e-d344-42e1-8185-4c5840429109,
  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 &lt;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 &lt;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. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.},
  author       = {de Vries, Paul S and V. Varga, Tibor and Franks, Paul and Morrison, Alanna C},
  issn         = {0002-9262},
  language     = {eng},
  number       = {6},
  pages        = {1033--1054},
  publisher    = {Oxford University Press},
  series       = {American Journal of Epidemiology},
  title        = {Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions},
  url          = {http://dx.doi.org/10.1093/aje/kwz005},
  doi          = {10.1093/aje/kwz005},
  volume       = {188},
  year         = {2019},
}