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dc.date.accessioned | 2019-03-13T13:32:09Z | |
dc.date.available | 2019-03-13T13:32:09Z | |
dc.date.issued | 2019-01-29 | |
dc.identifier.citation | Giulianini, F., et al. (2019). "Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions." | en_US |
dc.identifier.issn | 0002-9262 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/56171 | |
dc.description | This article has been accepted for publication in American Journal of Epidemiology . Published by Oxford University Press | 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.description.sponsorship | This work was supported by the National Heart, Lung, and Blood Institute grant R01HL118305. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756. American Heart Association Grant #17POST33350042 made it possible for Dr. de Vries to lead this project. | en_US |
dc.language | eng | |
dc.language.iso | en | en_US |
dc.publisher | Oxford University Press | en_US |
dc.relation.ispartof | Am J Epidemiol | |
dc.rights | This work is written by (a) US Government employee(s) and is in the public domain in the US | |
dc.subject | alcohol consumption | en_US |
dc.subject | cholesterol | en_US |
dc.subject | gene-environment interactions | en_US |
dc.subject | Gene-Lifestyle Interactions | en_US |
dc.subject | genome-wide association study | en_US |
dc.subject | ipid levels | en_US |
dc.subject | triglycerides | en_US |
dc.title | Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. | en_US |
dc.type | Article | en_US |
dc.rights.holder | Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019 | |
dc.identifier.doi | 10.1093/aje/kwz005 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30698716 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |