Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Ehret, G. B. et al. (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478(7367), pp. 103-109. (doi:10.1038/nature10405)

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Publisher's URL: http://dx.doi.org/10.1038/nature10405

Abstract

Blood pressure is a heritable trait1 influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥ 90 mm Hg diastolic blood pressure)2. Even small increments in blood pressure are associated with an increased risk of cardiovascular events3. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3–GUCY1B3,NPR3–C5orf23, ADM, FURIN–FES, GOSR2, GNAS–EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dominiczak, Professor Anna
Authors: Ehret, G. B., Munroe, P. B., Rice, K. M., Bochud, M., Johnson, A. D., Chasman, D. I., Smith, A. V., Tobin, M. D., Verwoert, G. C., Hwang, S.-J., Pihur, V., Vollenweider, P., O’Reilly, P. F., Amin, N., Bragg-Gresham, J. L., Teumer, A., Glazer, N. L., Launer, L., Hua Zhao, J., Aulchenko, Y., Heath, S., Sõber, S., Parsa, A., Luan, J.’a., Arora, P., Dehghan, A., Zhang, F., Lucas, G., Hicks, A. A., Jackson, A. U., Peden, J. F., Tanaka, T., Wild, S. H., Rudan, I., Igl, W., Milaneschi, Y., Parker, A. N., Fava, C., Chambers, J. C., Fox, E. R., Kumari, M., Jin Go, M., van der Harst, P., Hong Linda Kao, W., Sjögren, M., Vinay, D. G., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, P. H., Liu, Y., Shi, G., Kuusisto, J., Tayo, B., Seielstad, M., Sim, X., Hoang Nguyen, K.-D., Lehtimäki, T., Matullo, G., Wu, Y., Gaunt, T. R., Charlotte Onland-Moret, N., Cooper, M. N., Platou, C. G. P., Org, E., Hardy, R., Dahgam, S., Palmen, J., Vitart, V., Braund, P. S., Kuznetsova, T., Uiterwaal, C. S. P. M., Adeyemo, A., Palmas, W., Campbell, H., Ludwig, B., Tomaszewski, M., Tzoulaki, I., Palmer, N. D., Aspelund, T., Garcia, M., Chang, Y.-P. C., O’Connell, J. R., Steinle, N. I., Grobbee, D. E., Arking, D. E., Kardia, S. L., Morrison, A. C., Hernandez, D., Najjar, S., McArdle, W. L., Hadley, D., Brown, M. J., Connell, J. M., Hingorani, A. D., Day, I. N.M., Lawlor, D. A., Beilby, J. P., Lawrence, R. W., Clarke, R., Hopewell, J. C., Ongen, H., Dreisbach, A. W., Li, Y., Hunter Young, J., Bis, J. C., Kähönen, M., Viikari, J., Adair, L. S., Lee, N. R., Chen, M.-H., Olden, M., Pattaro, C., Hoffman Bolton, J. A., Köttgen, A., Bergmann, S., Mooser, V., Chaturvedi, N., Frayling, T. M., Islam, M., Jafar, T. H., Erdmann, J., Kulkarni, S. R., Bornstein, S. R., Grässler, J., Groop, L., Voight, B. F., Kettunen, J., Howard, P., Taylor, A., Guarrera, S., Ricceri, F., Emilsson, V., Plump, A., Barroso, I., Khaw, K.-T., Weder, A. B., Hunt, S. C., Sun, Y. V., Bergman, R. N., Collins, F. S., Bonnycastle, L. L., Scott, L. J., Stringham, H. M., Peltonen, L., Perola, M., Vartiainen, E., Brand, S.-M., Staessen, J. A., Wang, T. J., Burton, P. R., Soler Artigas, M., Dong, Y., Snieder, H., Wang, X., Zhu, H., Lohman, K. K., Rudock, M. E., Heckbert, S. R., Smith, N. L., Wiggins, K. L., Doumatey, A., Shriner, D., Veldre, G., Viigimaa, M., Kinra, S., Prabhakaran, D., Tripathy, V., Langefeld, C. D., Rosengren, A., Thelle, D. S., Maria Corsi, A., Singleton, A., Forrester, T., Hilton, G., McKenzie, C. A., Salako, T., Iwai, N., Kita, Y., Ogihara, T., Ohkubo, T., Okamura, T., Ueshima, H., Umemura, S., Eyheramendy, S., Meitinger, T., Wichmann, H.-E., Shin Cho, Y., Kim, H.-L., Lee, J.-Y., Scott, J., Sehmi, J. S., Zhang, W., Hedblad, B., Nilsson, P., Davey Smith, G., Wong, A., Narisu, N., Stančáková, A., Raffel, L. J., Yao, J., Kathiresan, S., O’Donnell, C. J., Schwartz, S. M., Arfan Ikram, M., Longstreth Jr, W. T., Mosley, T. H., Seshadri, S., Shrine, N. R.G., Wain, L. V., Morken, M. A., Swift, A. J., Laitinen, J., Prokopenko, I., Zitting, P., Cooper, J. A., Humphries, S. E., Danesh, J., Rasheed, A., Goel, A., Hamsten, A., Watkins, H., Bakker, S. J. L., van Gilst, W. H., Janipalli, C. S., Radha Mani, K., Yajnik, C. S., Hofman, A., Mattace-Raso, F. U. S., Oostra, B. A., Demirkan, A., Isaacs, A., Rivadeneira, F., Lakatta, E. G., Orru, M., Scuteri, A., Ala-Korpela, M., Kangas, A. J., Lyytikäinen, L.-P., Soininen, P., Tukiainen, T., Würtz, P., Twee-Hee Ong, R., Dörr, M., Kroemer, H. K., Völker, U., Völzke, H., Galan, P., Hercberg, S., Lathrop, M., Zelenika, D., Deloukas, P., Mangino, M., Spector, T. D., Zhai, G., Meschia, J. F., Nalls, M. A., Sharma, P., Terzic, J., Kranthi Kumar, M. V., Denniff, M., Zukowska-Szczechowska, E., Wagenknecht, L. E., Gerald R. Fowkes, F., Charchar, F. J., Schwarz, P. E. H., Hayward, C., Guo, X., Rotimi, C., Bots, M. L., Brand, E., Samani, N. J., Polasek, O., Talmud, P. J., Nyberg, F., Kuh, D., Laan, M., Hveem, K., Palmer, L. J., van der Schouw, Y. T., Casas, J. P., Mohlke, K. L., Vineis, P., Raitakari, O., Ganesh, S. K., Wong, T. Y., Shyong Tai, E., Cooper, R. S., Laakso, M., Rao, D. C., Harris, T. B., Morris, R. W., Dominiczak, A. F., Kivimaki, M., Marmot, M. G., Miki, T., Saleheen, D., Chandak, G. R., Coresh, J., Navis, G., Salomaa, V., Han, B.-G., Zhu, X., Kooner, J. S., Melander, O., Ridker, P. M., Bandinelli, S., Gyllensten, U. B., Wright, A. F., Wilson, J. F., Ferrucci, L., Farrall, M., Tuomilehto, J., Pramstaller, P. P., Elosua, R., Soranzo, N., Sijbrands, E. J. G., Altshuler, D., Loos, R. J. F., Shuldiner, A. R., Gieger, C., Meneton, P., Uitterlinden, A. G., Wareham, N. J., Gudnason, V., Rotter, J. I., Rettig, R., Uda, M., Strachan, D. P., Witteman, J. C. M., Hartikainen, A.-L., Beckmann, J. S., Boerwinkle, E., Vasan, R. S., Boehnke, M., Larson, M. G., Järvelin, M.-R., Psaty, B. M., Abecasis, G. R., Chakravarti, A., Elliott, P., van Duijn, C. M., Newton-Cheh, C., Levy, D., Caulfield, M. J., and Johnson, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature
Publisher:Nature Publishing Group
ISSN:0028-0836
ISSN (Online):1476-4687
Published Online:11 September 2011
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences