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

de Vries, P. S. et al. (2019) Multiancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions. American Journal of Epidemiology, 188(6), pp. 1033-1054. (doi: 10.1093/aje/kwz005) (PMID:30698716)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dominiczak, Professor Anna
• Authors: de Vries, P. S., Brown, M. R., Bentley, A. R., Sung, Y. J., Winkler, T. W., Ntalla, I., Schwander, K., Kraja, A. T., Guo, X., Franceschini, N., Cheng, C.-Y., Sim, X., Vojinovic, D., Huffman, J. E., Musani, S. K., Li, C., Feitosa, M. F., Richard, M. A., Noordam, R., Aschard, H., Bartz, T. M., Bielak, L. F., Deng, X., Dorajoo, R., Lohman, K. K., Manning, A. K., Rankinen, T., Smith, A. V., Tajuddin, S. M., Evangelou, E., Graff, M., Alver, M., Boissel, M., Chai, J. F., Chen, X., Divers, J., Gandin, I., Gao, C., Goel, A., Hagemeijer, Y., Harris, S. E., Hartwig, F. P., He, M., Horimoto, A. R. V. R., Hsu, F.-C., Jackson, A. U., Kasturiratne, A., Komulainen, P., Kühnel, B., Laguzzi, F., Lee, J. H., Luan, J.'a., Lyytikäinen, L.-P., Matoba, N., Nolte, I. M., Pietzner, M., Riaz, M., Said, M. A., Scott, R. A., Sofer, T., Stancáková, A., Takeuchi, F., Tayo, B. O., van der Most, P. J., Varga, T. V., Wang, Y., Ware, E. B., Wen, W., Yanek, L. R., Zhang, W., Zhao, J. H., Afaq, S., Amin, N., Amini, M., Arking, D. E., Aung, T., Ballantyne, C., Boerwinkle, E., Broeckel, U., Campbell, A., Canouil, M., Charumathi, S., Chen, Y.-D. I., Connell, J. M., de Faire, U., de Las Fuentes, L., de Mutsert, R., de Silva, H. J., Ding, J., Dominiczak, A. F., Duan, Q., Eaton, C. B., Eppinga, R. N., Faul, J. D., Fisher, V., Forrester, T., Franco, O. H., Friedlander, Y., Ghanbari, M., Giulianini, F., Grabe, H. J., Grove, M. L., Gu, C. C., Harris, T. B., Heikkinen, S., Heng, C.-K., Hirata, M., Hixson, J. E., Howard, B. V., Ikram, M. A., Jacobs, D. R., Johnson, C., Jonas, J. B., Kammerer, C. M., Katsuya, T., Khor, C. C., Kilpeläinen, T. O., Koh, W.-P., Koistinen, H. A., Kolcic, I., Kooperberg, C., Krieger, J. E., Kritchevsky, S. B., Kubo, M., Kuusisto, J., Lakka, T. A., Langefeld, C. D., Langenberg, C., Launer, L. J., Lehne, B., Lemaitre, R. N., Li, Y., Liang, J., Liu, J., Liu, K., Loh, M., Louie, T., Mägi, R., Manichaikul, A. W., McKenzie, C. A., Meitinger, T., Metspalu, A., Milaneschi, Y., Milani, L., Mohlke, K. L., Mosley, T. H., Mukamal, K. J., Nalls, M. A., Nauck, M., Nelson, C. P., Sotoodehnia, N., O'Connell, J. R., Palmer, N. D., Pazoki, R., Pedersen, N. L., Peters, A., Peyser, P. A., Polasek, O., Poulter, N., Raffel, L. J., Raitakari, O. T., Reiner, A. P., Rice, T. K., Rich, S. S., Robino, A., Robinson, J. G., Rose, L. M., Rudan, I., Schmidt, C. O., Schreiner, P. J., Scott, W. R., Sever, P., Shi, Y., Sidney, S., Sims, M., Smith, B. H., Smith, J. A., Snieder, H., Starr, J. M., Strauch, K., Tan, N., Taylor, K. D., Teo, Y. Y., Tham, Y. C., Uitterlinden, A. G., van Heemst, D., Vuckovic, D., Waldenberger, M., Wang, L., Wang, Y., Wang, Z., Wei, W. B., Williams, C., Wilson, G., Wojczynski, M. K., Yao, J., Yu, B., Yu, C., Yuan, J.-M., Zhao, W., Zonderman, A. B., Becker, D. M., Boehnke, M., Bowden, D. W., Chambers, J. C., Deary, I. J., Esko, T., Farrall, M., Franks, P. W., Freedman, B. I., Froguel, P., Gasparini, P., Gieger, C., Horta, B. L., Kamatani, Y., Kato, N., Kooner, J. S., Laakso, M., Leander, K., Lehtimäki, T., Magnusson, P. K. E., Penninx, B., Pereira, A. C., Rauramaa, R., Samani, N. J., Scott, J., Shu, X.-O., van der Harst, P., Wagenknecht, L. E., Wang, Y. X., Wareham, N. J., Watkins, H., Weir, D. R., Wickremasinghe, A. R., Zheng, W., Elliott, P., North, K. E., Bouchard, C., Evans, M. K., Gudnason, V., Liu, C.-T., Liu, Y., Psaty, B. M., Ridker, P. M., van Dam, R. M., Kardia, S. L. R., Zhu, X., Rotimi, C. N., Mook-Kanamori, D. O., Fornage, M., Kelly, T. N., Fox, E. R., Hayward, C., van Duijn, C. M., Tai, E. S., Wong, T. Y., Liu, J., Rotter, J. I., Gauderman, W. J., Province, M. A., Munroe, P. B., Rice, K., Chasman, D. I., Cupples, L. A., Rao, D. C., and Morrison, A. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Epidemiology
• Publisher: Oxford University Press
• ISSN: 0002-9262
• ISSN (Online): 1476-6256
• Published Online: 29 January 2019
• Copyright Holders: Copyright © 2019 Johns Hopkins Bloomberg School of Public Health
• First Published: First published in American Journal of Epidemiology 188(6):1033-1054
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher