Please use this identifier to cite or link to this item:
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.
ISSN: 0002-9262
Appears in Collections:Dept of Life Sciences Research Papers

Files in This Item:
File Description SizeFormat 
FullText.pdf311.71 kBAdobe PDFView/Open

Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.