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

Kato, Norihiro and Loh, Marie and Takeuchi, Fumihiko and Verweij, Niek and Wang, Xu and Zhang, Weihua and Kelly, Tanika N. and Saleheen, Danish and Lehne, Benjamin and Leach, Irene Mateo and Pinidiyapathirage, Mohitha J. (2015) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nature Genetics, 47 (11). pp. 1282-1293. ISSN 1061-4036

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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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to Published version, in accordance with the copyright policy of the publisher.
Faculty / Department / School: Current - Institute for Agriculture and the Environment
Date Deposited: 19 Apr 2016 04:31
Last Modified: 20 Nov 2017 23:27
Fields of Research : 06 Biological Sciences > 0604 Genetics > 060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases
Identification Number or DOI: 10.1038/ng.3405
URI: http://eprints.usq.edu.au/id/eprint/28699

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