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Nature Research, Nature Genetics, 11(47), p. 1282-1293, 2015

DOI: 10.1038/ng.3405

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

Journal article published in 2015 by Rob M. van Dam, Wiek H. van Gilst, Dirk J. van Veldhuisen, Joyce B. J. van Meurs, Pim van der Harst, Alexessander da Silva Couto Alves, dummy-Author_name, Norihiro Kato, T. NKelly, Marie Loh ORCID, Xu Wang, Irene Mateo Leach, Tanika N. Kelly, Alexander W. Drong, X. Wang and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

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 x 10(-11) to 5.0 x 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 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.