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

Article

Kato, Norihiro, Loh, Marie, Takeuchi, Fumihiko, Verweij, Niek, Wang, Xu, Zhang, Weihua, Kelly, Tanika N., Saleheen, Danish, Lehne, Benjamin, 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. https://doi.org/10.1038/ng.3405
Article Title

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

ERA Journal ID16629
Article CategoryArticle
AuthorsKato, Norihiro (Author), Loh, Marie (Author), Takeuchi, Fumihiko (Author), Verweij, Niek (Author), Wang, Xu (Author), Zhang, Weihua (Author), Kelly, Tanika N. (Author), Saleheen, Danish (Author), Lehne, Benjamin (Author), Leach, Irene Mateo (Author) and Pinidiyapathirage, Mohitha J. (Author)
Journal TitleNature Genetics
Journal Citation47 (11), pp. 1282-1293
Number of Pages12
Year2015
Place of PublicationUnited States
ISSN1061-4036
1546-1718
Digital Object Identifier (DOI)https://doi.org/10.1038/ng.3405
Web Address (URL)http://www.nature.com/doifinder/10.1038/ng.3405
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.

ANZSRC Field of Research 2020310505. Gene expression (incl. microarray and other genome-wide approaches)
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Byline AffiliationsNational Center for Global Health and Medicine, Japan
University of Oulu, Finland
University of Groningen, Netherlands
National University of Singapore
Imperial College London, United Kingdom
Tulane University, United States
Center for Non-Communicable Diseases, Pakistan
University of Kelaniya, Sri Lanka
Institution of OriginUniversity of Southern Queensland
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