Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

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Nat Genet. 2015 47 (11): 1282-1293

PMID: 26390057 · PMCID: PMC4719169 · DOI:10.1038/ng.3405

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.

MeSH Terms (22)

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

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