Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Feitosa, M. F. et al. (2018) Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. PLoS ONE, 13(6), e0198166. (doi: 10.1371/journal.pone.0198166) (PMID:29912962) (PMCID:PMC6005576)

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Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh
Creator Roles:
Padmanabhan, S.Data curation
Authors: Feitosa, M. F., Kraja, A. T., Chasman, D. I., Sung, Y. J., Winkler, T. W., Ntalla, I., Guo, X., Franceschini, N., Cheng, C.-Y., Sim, X., Vojinovic, D., Marten, J., Musani, S. K., Li, C., Bentley, A. R., Brown, M. R., Schwander, K., Richard, M. A., Noordam, R., Aschard, H., Bartz, T. M., Bielak, L. F., Dorajoo, R., Fisher, V., Hartwig, F. P., Horimoto, A. R. V. R., Lohman, K. K., Manning, A. K., Rankinen, T., Smith, A. V., Tajuddin, S. M., Wojczynski, M. K., Alver, M., Boissel, M., Cai, Q., Campbell, A., Chai, J. F., Chen, X., Divers, J., Gao, C., Goel, A., Hagemeijer, Y., Harris, S. E., He, M., Hsu, F.-C., Jackson, A. U., Kähönen, M., Kasturiratne, A., Komulainen, P., Kühnel, B., Laguzzi, F., Luan, J.'a., Matoba, N., Nolte, I. M., Padmanabhan, S., Riaz, M., Rueedi, R., Robino, A., Said, M. A., Scott, R. A., Sofer, T., Stančáková, A., Takeuchi, F., Tayo, B. O., van der Most, P. J., Varga, T. V., Vitart, V., Wang, Y., Ware, E. B., Warren, H. R., Weiss, S., Wen, W., Yanek, L. R., Zhang, W., Zhao, J. H., Afaq, S., Amin, N., Amini, M., Arking, D. E., Aung, T., Boerwinkle, E., Borecki, I., Broeckel, U., Brown, M., Brumat, M., Burke, G. L., Canouil, M., Chakravarti, A., Charumathi, S., Ida Chen, Y.-D., Connell, J. M., Correa, A., de Las Fuentes, L., de Mutsert, R., de Silva, H. J., Deng, X., Ding, J., Duan, Q., Eaton, C. B., Ehret, G., Eppinga, R. N., Evangelou, E., Faul, J. D., Felix, S. B., Forouhi, N. G., Forrester, T., Franco, O. H., Friedlander, Y., Gandin, I., Gao, H., Ghanbari, M., Gigante, B., Gu, C. C., Gu, D., Hagenaars, S. P., Hallmans, G., Harris, T. B., He, J., Heikkinen, S., Heng, C.-K., Hirata, M., Howard, B. V., Ikram, M. A., John, U., Katsuya, T., Khor, C. C., Kilpeläinen, T. O., Koh, W.-P., Krieger, J. E., Kritchevsky, S. B., Kubo, M., Kuusisto, J., Lakka, T. A., Langefeld, C. D., Langenberg, C., Launer, L. J., Lehne, B., Lewis, C. E., Li, Y., Lin, S., Liu, J., Liu, J., Loh, M., Louie, T., Mägi, R., McKenzie, C. A., Meitinger, T., Metspalu, A., Milaneschi, Y., Milani, L., Mohlke, K. L., Momozawa, Y., Nalls, M. A., Nelson, C. P., Sotoodehnia, N., Norris, J. M., O'Connell, J. R., Palmer, N. D., Perls, T., Pedersen, N. L., Peters, A., Peyser, P. A., Poulter, N., Raffel, L. J., Raitakari, O. T., Roll, K., Rose, L. M., Rosendaal, F. R., Rotter, J. I., Schmidt, C. O., Schreiner, P. J., Schupf, N., Scott, W. R., Sever, P. S., Shi, Y., Sidney, S., Sims, M., Sitlani, C. M., Smith, J. A., Snieder, H., Starr, J. M., Strauch, K., Stringham, H. M., Tan, N. Y. Q., Tang, H., Taylor, K. D., Teo, Y. Y., Tham, Y. C., Turner, S. T., Uitterlinden, A. G., Vollenweider, P., Waldenberger, M., Wang, L., Wang, Y. X., Wei, W. B., Williams, C., Yao, J., 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., Jonas, J. B., Kamatani, Y., Kato, N., Kooner, J. S., Kutalik, Z., Laakso, M., Laurie, C. C., Leander, K., Lehtimäki, T., Study, L. C., Magnusson, P. K. E., Oldehinkel, A. J., Penninx, B. W. J. H., Polasek, O., Porteous, D. J., Rauramaa, R., Samani, N. J., Scott, J., Shu, X.-O., van der Harst, P., Wagenknecht, L. E., Wareham, N. J., Watkins, H., Weir, D. R., Wickremasinghe, A. R., Wu, T., Zheng, W., Bouchard, C., Christensen, K., Evans, M. K., Gudnason, V., Horta, B. L., Kardia, S. L. R., Liu, Y., Pereira, A. C., Psaty, B. M., Ridker, P. M., van Dam, R. M., Gauderman, W. J., Zhu, X., Mook-Kanamori, D. O., Fornage, M., Rotimi, C. N., Cupples, L. A., Kelly, T. N., Fox, E. R., Hayward, C., van Duijn, C. M., Tai, E. S., Wong, T. Y., Kooperberg, C., Palmas, W., Rice, K., Morrison, A. C., Elliott, P., Caulfield, M. J., Munroe, P. B., Rao, D. C., Province, M. A., and Levy, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose
First Published:First published in PLoS ONE 13(6): e0198166
Publisher Policy:Reproduced under a Creative Commons License

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