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Title: | Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions |
Authors: | De Vries, PS Brown, MR Bentley, AR Sung, YJ Winkler, TW Ntalla, I Schwander, K Kraja, AT Guo, X Franceschini, N Cheng, CY Sim, X Vojinovic, D Huffman, JE Musani, SK Li, C Feitosa, MF Richard, MA Noordam, R Aschard, H Bartz, TM Bielak, LF Deng, X Dorajoo, R Lohman, KK Manning, AK Rankinen, T Smith, AV Tajuddin, SM Evangelou, E Graff, M Alver, M Boissel, M Chai, JF Chen, X Divers, J Gandin, I Gao, C Goel, A Hagemeijer, Y Harris, SE Hartwig, FP He, M Horimoto, ARVR Hsu, FC Jackson, AU Kasturiratne, A Komulainen, P Kühnel, B Laguzzi, F Lee, JH Luan, J Lyytikäinen, LP Matoba, N Nolte, IM Pietzner, M Riaz, M Said, MA Scott, RA Sofer, T Stančáková, A Takeuchi, F Tayo, BO Van Der Most, PJ Varga, TV Wang, Y Ware, EB Wen, W Yanek, LR Zhang, W Zhao, JH Afaq, S Amin, N Amini, M Arking, DE Aung, T Ballantyne, C Boerwinkle, E Broeckel, U Campbell, A Canouil, M Charumathi, S Chen, YDI Connell, JM De Faire, U De Las Fuentes, L De Mutsert, R De Silva, HJ Ding, J Dominiczak, AF Duan, Q Eaton, CB Eppinga, RN Faul, JD Fisher, V Forrester, T Franco, OH Friedlander, Y Ghanbari, M Giulianini, F |
Keywords: | alcohol consumption;cholesterol;gene-environment interactions;gene-lifestyle interactions;genome-wide association studies |
Issue Date: | 29-Jan-2019 |
Publisher: | Oxford University Press |
Citation: | American Journal of Epidemiology, 2019, 188 (6), pp. 1033 - 1054 |
Abstract: | © The Author(s) 2019. 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 × 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 × 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. |
URI: | http://bura.brunel.ac.uk/handle/2438/20681 |
DOI: | http://dx.doi.org/10.1093/aje/kwz005 |
ISSN: | 0002-9262 http://dx.doi.org/10.1093/aje/kwz005 1476-6256 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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