Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Surendran, P. et al. (2016) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nature Genetics, 48(10), pp. 1151-1161. (doi: 10.1038/ng.3654) (PMID:27618447) (PMCID:PMC5056636)

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High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension, and indicate new targets for clinical intervention.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and Menni, Ms Cristina and Young, Dr Robin and Caslake, Professor Muriel and Packard, Professor Chris and Sattar, Professor Naveed and Ford, Professor Ian
Authors: Surendran, P., Drenos, F., Young, R., Warren, H., Cook, J. P., Manning, A. K., Grarup, N., Sim, X., Barnes, D. R., Witkowska, K., Staley, J. R., Tragante, V., Tukiainen, T., Yahootkar, H., Masca, N., Freitag, D., Ferreira, T., Giannakopoulou, O., Tinker, A., Harakalova, M., Mihailov, E., Liu, C., Kraja, A. T., Nielsen, S. F., Rasheed, A., Samuel, M., Zhao, W., Bonnycastle, L. L., Jackson, A. U., Narisu, N., Swift, A. J., Southam, L., Marten, J., Huyghe, J. R., Stancáková, A., Fava, C., Ohlsson, T., Matchan, A., Stirrups, K. E., Bork-Jensen, J., Gjesing, A. P., Kontto, J., Perola, M., Shaw-Hawkins, S., Havulinna, A. S., Zhang, H., Donnelly, L. A., Groves, C., Rayner, N. W., Neville, M. J., Robertson, N. R., Yiorkas, A. M., Herzig, K.-H., Kajantie, E., Zhang, W., Willems, S. M., Lannfelt, L., Malerba, G., Soranzo, N., Trabetti, E., Verweij, N., Evangelou, E., Moayyeri, A., Vergnaud, C., Nelson, C. P., Poveda, A., Varga, T. V., Caslake, M., de'Craen, A. J.M., Trompet, S., Luan, J.'a., Scott, R. A., Harris, S. E., Liewald, D. C.M., Marioni, R., Menni, C., Farmaki, A.-E., Hallmans, G., Renström, F., Huffman, J. E., Hassinen, M., Burgess, S., Vasan, R. S., Felix, J. F., Uria-Nickelsen, M., Malarstig, A., Reily, D. F., Hoek, M., Vogt, T., Lin, H., Lieb, W., Traylor, M., Markus, H., Highland, H. M., Justice, A. E., Marouli, E., Lindström, J., Uusitupa, M., Komulainen, P., Lakka, T. A., Rauramaa, R., Polasek, O., Rudan, I., Rolandson, O., Franks, P. W., Dedoussis, G., Spector, T. D., Jousilahti, P., Männistö, S., Deary, I. J., Starr, J. M., Langenberg, C., Wareham, N. J., Brown, M. J., Dominiczak, A. F., Connell, J. M., Jukema, J. W., Sattar, N., Ford, I., Packard, C. J., Esko, T., Mägi, R., Metspalu, A., de Boer, R. A., van der Meer, P., van der Harst, P., Gambaro, G., Inglesson, E., Lind, L., de Bakker, P. I.W., Numan, M. E., Brandslund, I., Christensen, C., Petersen, E. R.B., Korpi-Hyövälti, E., Oksa, H., Chambers, J. C., Kooner, J. S., Blakemore, A. I.F., Franks, S., Jarvelin, M.-R., Husemoen, L. L., Linneberg, A., Skaaby, T., Thuesen, B., Karpe, F., Tuomilehto, J., Doney, A. S.F., Morris, A. D., Palmer, C. N.A., Holmen, O. L., Hveem, K., Willer, C. J., Tuomi, T., Groop, L., Käräjämäki, A., Palotie, A., Ripatti, S., Salomaa, V., Alam, D. S., al Shafi Majumder, A., Di Angelantonio, E., Chowdhury, R., McCarthy, M. I., Poulter, N., Stanton, A. V., Sever, P., Amouyel, P., Arveiler, D., Blankenberg, S., Ferrières, J., Kee, F., Kuulasmaa, K., Müller-Nurasyid, M., Veronesi, G., Virtamo, J., Deloukas, P., Elliott, P., Zeggini, E., Kathiresan, S., Melander, O., Kuusisto, J., Laakso, M., Padmanabhan, S., Porteous, D., Hayward, C., Collins, F. S., Mohlke, K. L., Hansen, T., Pedersen, O., Boehnke, M., Stringham, H. M., Frossard, P., Newton-Cheh, C., Tobin, M. D., Nordestgaard, B. G., Caulfield, M. J., Mahajan, A., Morris, A. P., Tomaszewski, M., Samani, N., Saleheen, D., Asselbergs, F. W., Morris, A. P., Tomaszewski, M., Samani, N. J., Saleheen, D., Asselbergs, F. W., Lindgren, C. M., Danesh, J., Wain, L. V., Butterworth, A. S., Howson, J. M.M., 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 > Robertson Centre
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN (Online):1546-1718
Published Online:12 September 2016
Copyright Holders:Copyright © 2016 Nature Publishing Group
First Published:First published in Nature Genetics 48(10): 1151-1161
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
174241United 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