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E. and Penninx, Brenda and Pereira, Alexandre C. and Rauramaa, Rainer and Samani, Nilesh J. and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E. and Wang, Ya Xing and Wareham, Nicholas J. and Watkins, Hugh and Weir, David R. and Wickremasinghe, Ananda R. and Zheng, Wei and Elliott, Paul and North, Kari E. and Bouchard, Claude and Evans, Michele K. and Gudnason, Vilmundur and Liu, Ching-Ti and Liu, Yongmei and Psaty, Bruce M. and Ridker, Paul M. and van Dam, Rob M. and Kardia, Sharon L. R. and Zhu, Xiaofeng and Rotimi, Charles N. and Mook-Kanamori, Dennis O. and Fornage, Myriam and Kelly, Tanika N. and Fox, Ervin R. and Hayward, Caroline and van Duijn, Cornelia M. and Tai, E. Shyong and Wong, Tien Yin and Liu, Jingmin and Rotter, Jerome I. and Gauderman, W. James and Province, Michael A. and Munroe, Patricia B. and Rice, Kenneth and Chasman, Daniel I. and Cupples, L. Adrienne and Rao, Dabeeru C. and Morrison, Alanna C. (2019) Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. AMERICAN JOURNAL OF EPIDEMIOLOGY, 188 (6). pp. 1033-1054. ISSN 0002-9262, 1476-6256
Full text not available from this repository. (Request a copy)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 < 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 Type: | Article |
|---|---|
| Uncontrolled Keywords: | DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; HDL CHOLESTEROL; LOW-FREQUENCY; BLOOD-LIPIDS; VEGF-B; METAANALYSIS; PLASMA; CONSUMPTION; INDIVIDUALS; alcohol consumption; cholesterol; gene-environment interactions; gene-lifestyle interactions; genome-wide association studies; lipids; triglycerides |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2020 05:59 |
| Last Modified: | 14 Apr 2020 05:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26884 |
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