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dc.date.accessioned |
2019-02-22T07:03:46Z |
|
dc.date.available |
2019-02-22T07:03:46Z |
|
dc.date.issued |
2019 |
|
dc.identifier.citation |
American Journal of Epidemiology.2019;188(6):1033–1054 |
en_US |
dc.identifier.issn |
0002-9262 (Print) |
|
dc.identifier.issn |
1476-6256 (Electronic) |
|
dc.identifier.uri |
http://repository.kln.ac.lk/handle/123456789/19987 |
|
dc.description |
indexed in Medline |
en_US |
dc.description.abstract |
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. |
en_US |
dc.language.iso |
en |
en_US |
dc.publisher |
School of Hygiene and Public Health of Johns Hopkins University,Baltimore. |
en_US |
dc.subject |
Gene-Alcohol interaction |
en_US |
dc.title |
Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions. |
en_US |
dc.type |
Article |
en_US |