Novel blood pressure locus and gene discovery using genome-wide association study and expression data sets from blood and the kidney

Wain, L. V. et al. (2017) Novel blood pressure locus and gene discovery using genome-wide association study and expression data sets from blood and the kidney. Hypertension, 70(3), e4-e19. (doi: 10.1161/HYPERTENSIONAHA.117.09438) (PMID:28739976)

Abstract

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

• Item Type: Articles
• Keywords: GWAS, blood pressure, cardiovascular risk, complex traits, eSNP, hypertension.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Padmanabhan, Professor Sandosh and Strawbridge, Dr Rona
• Authors: Wain, L. V., Vaez, A., Jansen, R., Joehanes, R., van der Most, P. J., Erzurumluoglu, A. M., O'Reilly, P. F., Cabrera, C. P., Warren, H. R., Rose, L. M., Verwoert, G. C., Hottenga, J.-J., Strawbridge, R. J., Esko, T., Arking, D. E., Hwang, S.-J., Guo, X., Kutalik, Z., Trompet, S., Shrine, N., Teumer, A., Ried, J. S., Bis, J. C., Smith, A. V., Amin, N., Nolte, I. M., Lyytikäinen, L.-P., Mahajan, A., Wareham, N. J., Hofer, E., Joshi, P. K., Kristiansson, K., Traglia, M., Havulinna, A. S., Goel, A., Nalls, M. A., Sõber, S., Vuckovic, D., Luan, J.'a., Del Greco M, F., Ayers, K. L., Marrugat, J., Ruggiero, D., Lopez, L. M., Niiranen, T., Enroth, S., Jackson, A. U., Nelson, C. P., Huffman, J. E., Zhang, W., Marten, J., Gandin, I., Harris, S. E., Zemunik, T., Lu, Y., Evangelou, E., Shah, N., de Borst, M. H., Mangino, M., Prins, B. P., Campbell, A., Li-Gao, R., Chauhan, G., Oldmeadow, C., Abecasis, G., Abedi, M., Barbieri, C. M., Barnes, M. R., Batini, C., Beilby, J., Blake, T., Boehnke, M., Bottinger, E. P., Braund, P. S., Brown, M., Brumat, M., Campbell, H., Chambers, J. C., Cocca, M., Collins, F., Connell, J., Cordell, H. J., Damman, J. J., Davies, G., de Geus, E. J., de Mutsert, R., Deelen, J., Demirkale, Y., Doney, A. S. F., Dörr, M., Farrall, M., Ferreira, T., Frånberg, M., Gao, H., Giedraitis, V., Gieger, C., Giulianini, F., Gow, A. J., Hamsten, A., Harris, T. B., Hofman, A., Holliday, E. G., Hui, J., Jarvelin, M.-R., Johansson, Å., Johnson, A. D., Jousilahti, P., Jula, A., Kähönen, M., Kathiresan, S., Khaw, K.-T., Kolcic, I., Koskinen, S., Langenberg, C., Larson, M., Launer, L. J., Lehne, B., Liewald, D. C. M., Lin, L., Lind, L., Mach, F., Mamasoula, C., Menni, C., Mifsud, B., Milaneschi, Y., Morgan, A., Morris, A. D., Morrison, A. C., Munson, P. J., Nandakumar, P., Nguyen, Q. T., Nutile, T., Oldehinkel, A. J., Oostra, B. A., Org, E., Padmanabhan, S., Palotie, A., Paré, G., Pattie, A., Penninx, B. W. J. H., Poulter, N., Pramstaller, P. P., Raitakari, O. T., Ren, M., Rice, K., Ridker, P. M., Riese, H., Ripatti, S., Robino, A., Rotter, J. I., Rudan, I., Saba, Y., Saint Pierre, A., Sala, C. F., Sarin, A.-P., Schmidt, R., Scott, R., Seelen, M. A., Shields, D. C., Siscovick, D., Sorice, R., Stanton, A., Stott, D. J., Sundström, J., Swertz, M., Taylor, K. D., Thom, S., Tzoulaki, I., Tzourio, C., Uitterlinden, A. G., Völker, U., Vollenweider, P., Wild, S., Willemsen, G., Wright, A. F., Yao, J., Thériault, S., Conen, D., Attia, J., Sever, P., Debette, S., Mook-Kanamori, D. O., Zeggini, E., Spector, T. D., van der Harst, P., Palmer, C. N. A., Vergnaud, A.-C., Loos, R. J. F., Polasek, O., Starr, J. M., Girotto, G., Hayward, C., Kooner, J. S., Lindgren, C. M., Vitart, V., Samani, N. J., Tuomilehto, J., Gyllensten, U., Knekt, P., Deary, I. J., Ciullo, M., Elosua, R., Keavney, B. D., Hicks, A. A., Scott, R. A., Gasparini, P., Laan, M., Liu, Y., Watkins, H., Hartman, C. A., Salomaa, V., Toniolo, D., Perola, M., Wilson, J. F., Schmidt, H., Zhao, J. H., Lehtimäki, T., van Duijn, C. M., Gudnason, V., Psaty, B. M., Peters, A., Rettig, R., James, A., Jukema, J. W., Strachan, D. P., Palmas, W., Metspalu, A., Ingelsson, E., Boomsma, D. I., Franco, O. H., Bochud, M., Newton-Cheh, C., Munroe, P. B., Elliott, P., Chasman, D. I., Chakravarti, A., Knight, J., Morris, A. P., Levy, D., Tobin, M. D., Snieder, H., Caulfield, M. J., and Ehret, G. B.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X
• ISSN (Online): 1524-4563
• Published Online: 24 July 2017
• Copyright Holders: Copyright © 2017 American Heart Association, Inc.
• First Published: First published in Hypertension 70(3): e4-e19
• Publisher Policy: Reproduced in accordance with the publisher copyright policy