The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Ehret, G. B. et al. (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics, 48(10), pp. 1171-1184. (doi:10.1038/ng.3667) (PMID:27618452) (PMCID:PMC5042863)

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Abstract

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Menni, Ms Cristina and Dominiczak, Professor Anna and Strawbridge, Dr Rona
Authors: Ehret, G. B., Ferreira, T., Chasman, D. I., Jackson, A. U., Schmidt, E. M., Johnson, T., Thorleifsson, G., Luan, J.'a., Donnelly, L. A., Kanoni, S., Petersen, A.-K., Pihur, V., Strawbridge, R. J., Shungin, D., Hughes, M. F., Meielles, O., Kaakinen, M., Bouatia-Naji, N., Kristiansson, K., Shah, S., Kleber, M. E., Guo, X., Lyytikäinen, L.-P., Fava, C., Eriksson, N., Nolte, I. M., Magnusson, P. K., Salfati, E. L., Rallidis, L. S., Theusch, E., Smith, A. J.P., Folkersen, L., Witkowska, K., Pers, T. H., Joehanes, R., Kim, S. K., Lataniotis, L., Jansen, R., Johnson, A. D., Warren, H., Kim, Y. J., Zhao, W., Wu, Y., Tayo, B. O., Bochud, M., Absher, D., Adair, L. S., Amin, N., Arking, D. E., Axelsson, T., Baldassarre, D., Balkau, B., Bandinelli, S., Barnes, M. R., Barroso, I., Bevan, S., Bis, J. C., Bjornsdottir, G., Boehnke, M., Boerwinkle, E., Bonnycastle, L. L., Boomsma, D. I., Bornstein, S. R., Brown, M. J., Burnier, M., Cabrera, C. P., Chambers, J. C., Chang, I.-S., Cheng, C.-Y., Chines, P. S., Chung, R.-H., Collins, F. S., Connell, J. M., Döring, A., Dallongeville, J., Danesh, J., de Faire, U., Delgado, G., Dominiczak, A. F., Doney, A. S.F., Drenos, F., Edkins, S., Eicher, J. D., Elosua, R., Enroth, S., Erdmann, J., Eriksson, P., Esko, T., Evangelou, E., Evans, A., Fall, T., Farrall, M., Felix, J. F., Ferrières, J., Ferrucci, L., Fornage, M., Forrester, T., Franceschini, N., Franco Duran, O. H., Franco-Cereceda, A., Fraser, R. M., Ganesh, S. K., Gao, H., Gertow, K., Gianfagna, F., Gigante, B., Giulianini, F., Goel, A., Goodall, A. H., Goodarzi, M. O., Gorski, M., Gräßler, J., Groves, C., Gudnason, V., Gyllensten, U., Halllmans, G., Hartikainn, A.-L., Hassinen, M., Havulinna, A. S., Hayward, C., Hercberg, S., Herzig, K.-H., Hicks, A. A., Hingorani, A. D., Hirschhorn, J. N., Hofman, A., Holmen, J., Holmen, O. L., Hottenga, J.-J., Howard, P., Hsiung, C. A., Hunt, S. C., Ikran, M. A., Illig, T., Iribarren, C., Jensen, R. A., Kähönen, M., Kang, H., Kathiresan, S., Keating, B. J., Khaw, K.-T., Kim, Y. K., Kim, E., Kivimaki, M., Klopp, N., Kolovou, G., Komulainen, P., Kooner, J. S., Kosova, G., Krauss, R. M., Kuh, D., Kutalik, Z., Kuusisto, J., Kvaløy, K., Lakka, T. A., Lee, N. R., Lee, I.-T., Lee, W.-J., Levy, D., Li, X., Liang, K.-W., Lin, H., Lin, L., Lindström, J., Lobbens, S., Männistö, S., Müller, G., Müller-Nurasyid, M., Mach, F., Markus, H. S., Marouli, E., McCarthy, M. I., McKenzie, C. A., Meneton, P., Menni, C., Metspalu, A., Mijatovic, V., Moilanen, L., Montasser, M. E., Morris, A. D., Morrison, A. C., Mulas, A., Nagaraja, R., Narisu, N., Nikus, K., O'Donnell, C. J., O'Reilly, P. F., Ong, K. K., Paccaud, F., Palmer, C. D., Parsa, A., Pedersen, N. L., Penninx, B. W., Perola, M., Peters, A., Poulter, N., Pramstaller, P. P., Psaty, B. M., Quertermous, T., Rao, D. C., Rasheed, A., Rayner, N. W. N.W.R., Renström, F., Rettig, R., Rice, K. M., Roberts, R., Rose, L. M., Rossouw, J., Samani, N. J., Sanna, S., Saramies, J., Schunkert, H., Sebert, S., Sheu, W. H.-H., Shin, Y.-A., Sim, X., Smit, J. H., Smith, A. V., Sosa, M. X., Spector, T. D., Stančáková, A., Stanton, A., Stirrups, K. E., Stringham, H. M., Sundstrom, J., Swift, A. J., Syvänen, A.-C., Tai, E.-S., Tanaka, T., Tarasov, K. V., Teumer, A., Thorsteinsdottir, U., Tobin, M. D., Tremoli, E., Uitterlinden, A. G., Uusitupa, M., Vaez, A., Vaidya, D., van Duijn, C. M., van Iperen, E. P.A., Vasan, R. S., Verwoert, G. C., Virtamo, J., Vitart, V., Voight, B. F., Vollenweider, P., Wagner, A., Wain, L. V., Wareham, N. J., Watkins, H., Weder, A. B., Westra, H.-J., Wilks, R., Wilsgaard, T., Wilson, J. F., Wong, T. Y., Yang, T.-P., Yao, J., Yengo, L., Zhang, W., Zhao, J. H., Zhu, X., Bovet, P., Cooper, R. S., Mohlke, K. L., Saleheen, D., Lee, J.-Y., Elliott, P., Gierman, H. J., Willer, C. J., Franke, L., Hovingh, G. K., Taylor, K. D., Dedoussis, G., Sever, P., Wong, A., Lind, L., Assimes, T., Njølstad, I., Schwarz, P. E.H., Langenberg, C., Snieder, H., Caulfield, M. J., Melander, O., Laakso, M., Saltevo, J., Rauramaa, R., Tuomilehto, J., Ingelsson, E., Lehtimäki, T., Hveem, K., Palmas, W., März, W., Kumari, M., Salomaa, V., Chen, Y.-D. I., Rotter, J. I., Froguel, P., Jarvelin, M.-R., Lakatta, E. G., Kuulasmaa, K., Franks, P. W., Hamsten, A., Wichmann, H.-E., Palmer, C. N.A., Stefansson, K., Ridker, P. M., Loos, R. J.F., Chakravarti, A., Deloukas, P., Morris, A. P., Newton-Cheh, C., and Munroe, P. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:12 September 2016
Copyright Holders:Copyright © 2016 Nature America, Inc.
First Published:First published in Nature Genetics 48(10):1171-1184
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
174244United Kingdom Collaborative Study to Identify the Major Genes Responsible for Human Essential Hypertension (BRIGHT)John ConnellMedical Research Council (MRC)G9521010SCHOOL OF MEDICINE, DENTISTRY & NURSING
348311The British genetics of hypertension study - application to enhance TDT and control recruitment for fine mapping genes for hypertensionAnna DominiczakBritish Heart Foundation (BHF)PG/02/128 MCPG1RI CARDIOVASCULAR & MEDICAL SCIENCES
464051Genomics and proteomics of hypertension and its vascular complications: the pathwayomic strategies.Anna DominiczakBritish Heart Foundation (BHF)RG/07/005/23633RI CARDIOVASCULAR & MEDICAL SCIENCES
483571Collaborative strategy for a definitive genome scan in essential hypertension: high fidelity phenotyping and "hypercontrols"Anna DominiczakBritish Heart Foundation (BHF)SP/08/005/25115RI CARDIOVASCULAR & MEDICAL SCIENCES
421221InGenious HyperCare - Integrating Genomics, Clinical Research and Care in HypertensionAnna DominiczakEuropean Commission (EC)LSHM-CT-2006-03RI CARDIOVASCULAR & MEDICAL SCIENCES
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS