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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123665.pdf - Accepted Version 5MB |
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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Health & 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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