Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

Xiangfeng Lu, Laiyuan Wang, Xu Lin, Jianfeng Huang, C. Charles gu, Meian He, Hongbing Shen, Jiang He, Jingwen Zhu, Huaixing Li, James E. Hixson, Tangchun Wu, Juncheng Dai, Ling Lu, Chong Shen, Shufeng Chen, Lin He, Zengnan Mo, Yongchen Hao, Xingbo MoXueli Yang, Jianxin Li, Jie Cao, Jichun Chen, Zhongjie Fan, Ying Li, Liancheng Zhao, Hongfan Li, Fanghong Lu, Cailiang Yao, Lin Yu, Lihua Xu, Jianjun Mu, Xianping Wu, Ying Deng, Dongsheng Hu, Weidong Zhang, Xu Ji, Dongshuang Guo, Zhirong Guo, Zhengyuan Zhou, Zili Yang, Renping Wang, Jun Yang, Xiaoyang Zhou, Weili Yan, Ninglingh Sun, Pingjin Gao, Dongfeng Gu

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10-8) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10-3 to 5.16 × 10-8. These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

Original languageEnglish
Pages (from-to)865-874
Number of pages10
JournalHuman molecular genetics
Volume24
Issue number3
DOIs
StatePublished - Feb 1 2015

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