Lu Xiangfeng, Wang Laiyuan, Lin Xu, Huang Jianfeng, Charles Gu C, He Meian, Shen Hongbing, He Jiang, Zhu Jingwen, Li Huaixing, Hixson James E, Wu Tangchun, Dai Juncheng, Lu Ling, Shen Chong, Chen Shufeng, He Lin, Mo Zengnan, Hao Yongchen, Mo Xingbo, Yang Xueli, Li Jianxin, Cao Jie, Chen Jichun, Fan Zhongjie, Li Ying, Zhao Liancheng, Li Hongfan, Lu Fanghong, Yao Cailiang, Yu Lin, Xu Lihua, Mu Jianjun, Wu Xianping, Deng Ying, Hu Dongsheng, Zhang Weidong, Ji Xu, Guo Dongshuang, Guo Zhirong, Zhou Zhengyuan, Yang Zili, Wang Renping, Yang Jun, Zhou Xiaoyang, Yan Weili, Sun Ningling, Gao Pingjin, Gu Dongfeng
State Key Laboratory of Cardiovascular Disease Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
State Key Laboratory of Cardiovascular Disease National Human Genome Center at Beijing, Beijing 100176, China.
Hum Mol Genet. 2015 Feb 1;24(3):865-74. doi: 10.1093/hmg/ddu478. Epub 2014 Sep 23.
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.
高血压是一种常见疾病，也是全球心血管疾病和过早死亡的主要危险因素。欧洲人群的全基因组关联研究（GWAS）已确定了多个与血压相关的染色体区域，但所确定的基因座总共仅解释了血压变异的一小部分。中国和欧洲人群在环境暴露和遗传背景方面的差异可能表明血压调节存在潜在的不同途径。为了识别影响血压变异的新遗传变异，我们对11816名受试者的血压和高血压GWAS进行了荟萃分析，随后进行了包括另外69146名个体的重复研究。我们确定了与血压具有全基因组显著性（P < 5.0 × 10^(-8)）的关联，其中包括三个新基因座（CACNA1D、CYP21A2和MED13L）的变异以及SLC4A7附近新发现的一个变异。我们还重复验证了14个先前报道的基因座，其中8个（CASZ1、MOV10、FGF5、CYP17A1、SOX6、ATP2B1、ALDH2和JAG1）达到全基因组显著性，6个（FIGN、ULK4、GUCY1A3、HFE、TBX3 - TBX5和TBX3）达到P = 1.81 × 10^(-3)至5.16 × 10^(-8)的提示性水平。这些发现为血压调节提供了新的机制见解和潜在的治疗靶点。
