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We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Original publication

DOI

10.1038/ng.3405

Type

Journal article

Journal

Nature genetics

Publication Date

11/2015

Volume

47

Pages

1282 - 1293

Addresses

Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

Keywords

BIOS-consortium, CARDIo GRAMplusCD, LifeLines Cohort Study, InterAct Consortium, Humans, Cardiovascular Diseases, Genetic Predisposition to Disease, Natriuretic Peptide, Brain, Peptide Fragments, Risk Factors, Regression Analysis, DNA Methylation, Blood Pressure, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Genetic Variation, Genome-Wide Association Study, Genetic Loci