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Multiancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions

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...

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Main Authors: Vries, Paul S. de (Author) , Brown, Michael R. (Author) , Bentley, Amy R. (Author) , Sung, Yun J. (Author) , Winkler, Thomas W. (Author) , Ntalla, Ioanna (Author) , Schwander, Karen (Author) , Kraja, Aldi T. (Author) , Guo, Xiuqing (Author) , Franceschini, Nora (Author) , Cheng, Ching-Yu (Author) , Sim, Xueling (Author) , Vojinovic, Dina (Author) , Huffman, Jennifer E. (Author) , Musani, Solomon K. (Author) , Li, Changwei (Author) , Feitosa, Mary F. (Author) , Richard, Melissa A. (Author) , Noordam, Raymond (Author) , Aschard, Hugues (Author) , Jonas, Jost B. (Author)
Format: Article (Journal)
Language:English
Published: January 29, 2019
In: American journal of epidemiology
Year: 2019, Volume: 188, Issue: 6, Pages: 1033-1054
ISSN:1476-6256
DOI:10.1093/aje/kwz005
Online Access:Verlag, Volltext: https://doi.org/10.1093/aje/kwz005
Verlag, Volltext: https://academic.oup.com/aje/article/188/6/1033/5304469
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Author Notes:Paul S. de Vries, Michael R. Brown, Amy R. Bentley, Yun J. Sung, Thomas W. Winkler, Ioanna Ntalla, Karen Schwander, Aldi T. Kraja, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jennifer E. Huffman, Solomon K. Musani, Changwei Li, Mary F. Feitosa, Melissa A. Richard, Raymond Noordam, Hugues Aschard et al.
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Summary: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.
Item Description:Gesehen am 04.10.2019
Physical Description:Online Resource
ISSN:1476-6256
DOI:10.1093/aje/kwz005

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