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Title: Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
Authors: Kato, Norihiro
Loh, Marie
Takeuchi, Fumihiko
Verweij, Niek
Wang, Xu 
Zhang, Weihua
Kelly, Tanika N.
Saleheen, Danish
Lehne, Benjamin
Leach, Irene Mateo
Khor, Chiea-Chuen 
Mok, Zuan Yu 
Sapari, Nur Sabrina
Teh, Ai Ling
Cheng, Ching-Yu 
Chong, Yap Seng 
Koh, Woon-Puay 
Lee, Jen-Mai Jeannette 
Liao, Jiemin 
Van Dam, Rob Martinus 
Wong, Tien-Yin 
Liu, Jianjun 
Vithana, Eranga Nishanthie 
Teo, Yik-Ying 
Tai, E. Shyong 
Issue Date: 1-Nov-2015
Publisher: Nature Publishing Group
Citation: Kato, Norihiro, Loh, Marie, Takeuchi, Fumihiko, Verweij, Niek, Wang, Xu, Zhang, Weihua, Kelly, Tanika N., Saleheen, Danish, Lehne, Benjamin, Leach, Irene Mateo, Khor, Chiea-Chuen, Mok, Zuan Yu, Sapari, Nur Sabrina, Teh, Ai Ling, Cheng, Ching-Yu, Chong, Yap Seng, Koh, Woon-Puay, Lee, Jen-Mai Jeannette, Liao, Jiemin, Van Dam, Rob Martinus, Wong, Tien-Yin, Liu, Jianjun, Vithana, Eranga Nishanthie, Teo, Yik-Ying, Tai, E. Shyong (2015-11-01). Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nature Genetics 47 (11) : 1282-1293. ScholarBank@NUS Repository.
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.
Source Title: Nature Genetics
ISSN: 10614036
DOI: 10.1038/ng.3405
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