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

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 valida...

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Detalles Bibliográficos
Autores principales: Warren, Helen R, Evangelou, Evangelos, Cabrera, Claudia P, Gao, He, Ren, Meixia, Mifsud, Borbala, Ntalla, Ioanna, Surendran, Praveen, Liu, Chunyu, Cook, James P, Kraja, Aldi T, Drenos, Fotios, Loh, Marie, Verweij, Niek, Marten, Jonathan, Karaman, Ibrahim, Segura Lepe, Marcelo P, O’Reilly, Paul F, Knight, Joanne, Snieder, Harold, Kato, Norihiro, He, Jiang, Tai, E Shyong, Said, M Abdullah, Porteous, David, Alver, Maris, Poulter, Neil, Farrall, Martin, Gansevoort, Ron T, Padmanabhan, Sandosh, Mägi, Reedik, Stanton, Alice, Connell, John, Bakker, Stephan J L, Metspalu, Andres, Shields, Denis C, Thom, Simon, Brown, Morris, Sever, Peter, Esko, Tõnu, Hayward, Caroline, van der Harst, Pim, Saleheen, Danish, Chowdhury, Rajiv, Chambers, John C, Chasman, Daniel I, Chakravarti, Aravinda, Newton-Cheh, Christopher, Lindgren, Cecilia M, Levy, Daniel, Kooner, Jaspal S, Keavney, Bernard, Tomaszewski, Maciej, Samani, Nilesh J, Howson, Joanna M M, Tobin, Martin D, Munroe, Patricia B, Ehret, Georg B, Wain, Louise V, Barnes, Michael R, Tzoulaki, Ioanna, Caulfield, Mark J, Elliott, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972004/
https://www.ncbi.nlm.nih.gov/pubmed/28135244
http://dx.doi.org/10.1038/ng.3768
Descripción
Sumario: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. Combined 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.

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