Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2015-11-01
Date Acceptance
2015-08-21
Citation
Nature Genetics, 2015, 47 (11), pp.1282-1293
ISSN
1546-1718
Publisher
Nature Publishing Group
Start Page
1282
End Page
1293
Journal / Book Title
Nature Genetics
Volume
47
Issue
11
Copyright Statement
© 2015, Rights Managed by Nature Publishing Group
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
PULMONARY ARTERIAL-HYPERTENSION
CENTRIC ARRAY
RISK-FACTORS
CARDIOVASCULAR-DISEASE
VARIANTS
REGIONS
KIDNEY
TISSUE
METAANALYSIS
INDIVIDUALS
Publication Status
Published
Date Publish Online
2015-09-21