Nature Genetics, 2015, 01, 1282─1293

Trans-ancestry gwas identifies 12 genetic loci influencing bp and implicates a role for DNA methylation

NKato, MLoh, FTakeuchi, NVerweij, Yik-Ying Teo, Jiang He, Paul Elliott, E Shyong Tai, Pim van der Harst, Jaspal S Kooner, John C Chambers

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.

• ISBN or ISSN: 1061-4036

• 본 연구는 질병관리본부 연구개발과제(과제번호 2012-N73002-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2012-N73002-00) by Research of Korea Centers for Disease Control and Prevention.