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

Georg B. Ehret, Patricia B. Munroe, Kenneth M. Rice, Murielle Bochud, Andrew D. Johnson, Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih-Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F. O'Reilly, Najaf Amin, Jennifer L. Bragg-Gresham, Alexander Teumer, Nicole L. Glazer, Lenore Launer, Jing Hua Zhao, Yurii AulchenkoSimon Heath, Siim Sober, Afshin Parsa, Jian'an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne U. Jackson, John F. Peden, Toshiko Tanaka, Sarah H. Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N. Parker, Cristiano Fava, John C. Chambers, Ervin R. Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjogren, D. G. Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, John M. Connell, CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium

    Research output: Contribution to journalArticle

    1330 Citations (Scopus)

    Abstract

    Blood pressure is a heritable trait(1) 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 events(3). 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.

    Original languageEnglish
    Pages (from-to)103-109
    Number of pages7
    JournalNature
    Volume478
    Issue number7367
    DOIs
    Publication statusPublished - 6 Oct 2011

    Keywords

    • GENOME-WIDE ASSOCIATION
    • COMMON VARIANTS
    • HYPERTENSION
    • METAANALYSIS
    • LOCI
    • POPULATION
    • RELEVANCE
    • RECEPTOR
    • CLONING
    • HEALTH

    Cite this

    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., Zhao, J. H., ... CARDIoGRAM Consortium, KidneyGen Consortium, EchoGen Consortium, CKDGen Consortium, Int Consortium Blood Pressure Geno, CHARGE-HF Consortium (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478(7367), 103-109. https://doi.org/10.1038/nature10405