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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Abstract
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 |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and Menni, Ms Cristina and Caslake, Professor Muriel and Young, Dr Robin 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre |
| 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 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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