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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
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2019 (Engelska)Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, nr 6, s. 1033-1054Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 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 stages 1 and 2, a total of 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 (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.

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Oxford University Press, 2019. Vol. 188, nr 6, s. 1033-1054
Nyckelord [en]
alcohol consumption, cholesterol, gene-environment interactions, gene-lifestyle interactions, genome-wide association studies, lipids, triglycerides
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
URN: urn:nbn:se:umu:diva-161740DOI: 10.1093/aje/kwz005ISI: 000473760200007PubMedID: 30698716OAI: oai:DiVA.org:umu-161740DiVA, id: diva2:1339146
Tillgänglig från: 2019-07-26 Skapad: 2019-07-26 Senast uppdaterad: 2019-07-26Bibliografiskt granskad

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Franks, Paul W.

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Tajuddin, Salman M.Boissel, MathildeChen, XuHagemeijer, YanickSaid, M. AbdullahSofer, TamarVarga, Tibor V.Canouil, MickaelHeikkinen, SamiKammerer, Candace M.Li, YizeSmith, Jennifer A.Waldenberger, MelanieFranks, Paul W.Froguel, PhilippeLiu, Ching-TiZhu, Xiaofeng
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American Journal of Epidemiology
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