Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
Article
Article Title | Trans-ancestry genome-wide association study identifies |
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ERA Journal ID | 16629 |
Article Category | Article |
Authors | Kato, 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 Title | Nature Genetics |
Journal Citation | 47 (11), pp. 1282-1293 |
Number of Pages | 12 |
Year | 2015 |
Place of Publication | United States |
ISSN | 1061-4036 |
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 2020 | 310505. Gene expression (incl. microarray and other genome-wide approaches) |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | National 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 Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q3549/trans-ancestry-genome-wide-association-study-identifies-12-genetic-loci-influencing-blood-pressure-and-implicates-a-role-for-dna-methylation
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