| Title | Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | de Vries, PS, Brown, MR, Bentley, AR, Sung, YJ, Winkler, TW, Ntalla, I, Schwander, K, Kraja, AT, Guo, X, Franceschini, N, Cheng, C-Y, 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, JFang, Chen, X, Divers, J, Gandin, I, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, Hartwig, FP, He, M, Horimoto, ARVR, Hsu, F-C, Jackson, AU, Kasturiratne, A, Komulainen, P, Kuhnel, B, Laguzzi, F, Lee, JH, Luan, J'an, Lyytikäinen, L-P, Matoba, N, Nolte, IM, Pietzner, M, Riaz, M, M Said, A, 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, Y-DI, Connell, JM, de Faire, U, Fuentes, Lde Las, de Mutsert, R, H de Silva, J, Ding, J, Dominiczak, AF, Duan, Q, Eaton, CB, Eppinga, RN, Faul, JD, Fisher, V, Forrester, T, Franco, OH, Friedlander, Y, Ghanbari, M, Giulianini, F, Grabe, HJ, Grove, ML, C Gu, C, Harris, TB, Heikkinen, S, Heng, C-K, Hirata, M, Hixson, JE, Howard, BV, Ikram, AM, Jacobs, DR, Johnson, C, Jonas, JBruno, Kammerer, CM, Katsuya, T, Khor, CChuen, Kilpeläinen, TO, Koh, W-P, Koistinen, HA, Kolcic, I, Kooperberg, C, Krieger, JE, Kritchevsky, SB, Kubo, M, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lehne, B, Lemaitre, RN, Li, Y, Liang, J, Liu, J, Liu, K, Loh, M, Louie, T, Mägi, R, Manichaikul, AW, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, KL, Mosley, TH, Mukamal, KJ, Nalls, MA, Nauck, M, Nelson, CP, Sotoodehnia, N, O'Connell, JR, Palmer, ND, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Poulter, N, Raffel, LJ, Raitakari, OT, Reiner, AP, Rice, TK, Rich, SS, Robino, A, Robinson, JG, Rose, LM, Rudan, I, Schmidt, CO, Schreiner, PJ, Scott, WR, Sever, P, Shi, Y, Sidney, S, Sims, M, Smith, BH, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Tan, N, Taylor, KD, Teo, YYing, Tham, YChung, Uitterlinden, AG, van Heemst, D, Vuckovic, D, Waldenberger, M, Wang, L, Wang, Y, Wang, Z, Bin Wei, W, Williams, C, Wilson, G, Wojczynski, MK, Yao, J, Yu, B, Yu, C, Yuan, J-M, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Deary, IJ, Esko, T, Farrall, M, Franks, PW, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Horta, BL, Kamatani, Y, Kato, N, Kooner, JS, Laakso, M, Leander, K, Lehtimäki, T, Magnusson, PKE, Penninx, B, Pereira, AC, Rauramaa, R, Samani, NJ, Scott, J, Shu, X-O, van der Harst, P, Wagenknecht, LE, Wang, YXing, Wareham, NJ, Watkins, H, Weir, DR, Wickremasinghe, AR, Zheng, W, Elliott, P, North, KE, Bouchard, C, Evans, MK, Gudnason, V, Liu, C-T, Liu, Y, Psaty, BM, Ridker, PM, van Dam, RM, Kardia, SLR, Zhu, X, Rotimi, CN, Mook-Kanamori, DO, Fornage, M, Kelly, TN, Fox, ER, Hayward, C, van Duijn, CM, Tai, SE, Wong, TYin, Liu, J, Rotter, JI, W Gauderman, J, Province, MA, Munroe, PB, Rice, K, Chasman, DI, Cupples, AL, Rao, DC, Morrison, AC |
| Corporate/Institutional Authors | InterAct Consortium, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study) |
| Journal | Am J Epidemiol |
| Date Published | 2019 Jan 29 |
| ISSN | 1476-6256 |
| Abstract | <p>An individual'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 multi-ancestry 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 five ancestry groups. Genetic main and interaction effects were jointly assessed by 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 Stage 1 and Stage 2, 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 (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.</p> |
| DOI | 10.1093/aje/kwz005 |
| Alternate Journal | Am. J. Epidemiol. |
| PubMed ID | 30698716 |
| Grant List | G0700931 / / Medical Research Council / United Kingdom
MR/L01632X/1 / / Medical Research Council / United Kingdom
R01 HL142302 / HL / NHLBI NIH HHS / United States
MR/L01341X/1 / / Medical Research Council / United Kingdom
G0601966 / / Medical Research Council / United Kingdom
MC_UU_12015/1 / / Medical Research Council / United Kingdom |
