Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Warren, H. R. et al. (2017) Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nature Genetics, 49(3), pp. 403-415. (doi: 10.1038/ng.3768) (PMID:28135244) (PMCID:PMC5972004)

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Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure–raising genetic variants on future cardiovascular disease risk.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh and Stott J, Professor David
Authors: Warren, H. R., Evangelou, E., Cabrera, C. P., Gao, H., Ren, M., Mifsud, B., Ntalla, I., Surendran, P., Liu, C., Cook, J. P., Kraja, A. T., Drenos, F., Loh, M., Verweij, N., Marten, J., Karaman, I., Lepe, M. P. S., O'Reilly, P. F., Knight, J., Snieder, H., Kato, N., He, J., Tai, E. S., Said, M. A., Porteous, D., Alver, M., Poulter, N., Farrall, M., Gansevoort, R. T., Padmanabhan, S., Mägi, R., Stanton, A., Connell, J., Bakker, S. J.L., Metspalu, A., Shields, D. C., Thom, S., Brown, M., Sever, P., Esko, T., Hayward, C., van der Harst, P., Saleheen, D., Chowdhury, R., Chambers, J. C., Chasman, D. I., Chakravarti, A., Newton-Cheh, C., Lindgren, C. M., Levy, D., Kooner, J. S., Keavney, B., Tomaszewski, M., Samani, N. J., Howson, J. M.M., Tobin, M. D., Munroe, P. B., Ehret, G. B., Wain, L. V., Barnes, M. R., Tzoulaki, I., Caulfield, M. J., Elliott, P., and Stott, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:30 January 2017
Copyright Holders:Copyright © 2017 Nature America, Inc., part of Springer Nature
First Published:First published in Nature Genetics 49(3): 403-415
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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