Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
Nature genetics 2015 ; 47: 1282-1293.
Verweij N, Zhang W, Saleheen D, Lehne B, Wahl S, Scott WR, Afzal U, Ahluwalia TS, Esko T, Harris SE, Saxena R, Stolk L, Luan J, Scott RA, Sorice R, Traglia M, Zhang Y, Barroso I, Bjonnes A, Davies G, Gansevoort RT, Grarup N, Hofman A, Liewald DCM, Meitinger T, Mihailov E, Milani L, Müller-Nurasyid M, Nutile T, Peters A, Rolandsson O, Ruggiero D, Sala CF, Snieder H, Starr JM, Trompet S, Uitterlinden AG, van Dam RM, Waldenberger M, Asselbergs FW, Ciullo M, Deloukas P, Franks PW, Hansen T, Järvelin MR, Jørgensen T, Jukema JW, Kähönen M, Lehtimäki T, Linneberg A, Pedersen O, Samani NJ, Sørensen TIA, Toniolo D, Danesh J, Deary IJ, Franco OH, Franke L, Metspalu A, Mohlke KL, Sanghera DK, Zheng W, Vineis P, McCarthy MI, Gieger C, van der Harst P, Kooner JS, and Chambers JC
DOI : 10.1038/ng.3405
PubMed ID : 26390057
PMCID : EMS66668
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.