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 Mo; Xueli 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

doi:10.1093/hmg/ddu478

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 Mo

Xueli 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

Health Science Center

Chinese Academy of Medical Sciences
Chinese National Human Genome Center
CAS - Shanghai Institute of Nutrition and Health
Washington University St. Louis
Huazhong University of Science and Technology
Nanjing Medical University
Tulane University
University of Texas Health Science Center at Houston
Shanghai Jiao Tong University
Guangxi Medical University
Shandong First Medical University & Shandong Academy of Medical Sciences
Fujian Provincial Hospital
Beihua University
Sichuan Center of Disease Control and Prevention
Zhengzhou University
Shenzhen University
Xinle Red Cross Hospital
Yuxian Renmin Hospital
Soochow University
Changshu Center of Disease Control and Prevention
Nantong Center of Disease Control and Prevention
Shijiazhuang Greatwall Hospital
Hanzhong People's Hospital
Renmin Hospital of Wuhan University
Children's Hospital of Fudan University
Peking University

Research output: Contribution to journal › Article › peer-review

171 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 language	English
Pages (from-to)	865-874
Number of pages	10
Journal	Human Molecular Genetics
Volume	24
Issue number	3
DOIs	https://doi.org/10.1093/hmg/ddu478
State	Published - 1 Feb 2015

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SDG 3 Good Health and Well-being

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10.1093/hmg/ddu478

Cite this

Lu, X., Wang, L., Lin, X., Huang, J., Charles gu, C., He, M., Shen, H., He, J., Zhu, J., Li, H., Hixson, J. E., Wu, T., Dai, J., Lu, L., Shen, C., Chen, S., He, L., Mo, Z., Hao, Y., ... Gu, D. (2015). Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension. Human Molecular Genetics, 24(3), 865-874. https://doi.org/10.1093/hmg/ddu478

@article{c267b7633b3944fb887dee8890ee28d1,

title = "Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension",

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 {\texttimes} 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 {\texttimes} 10-3 to 5.16 {\texttimes} 10-8. These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.",

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

year = "2015",

month = feb,

day = "1",

doi = "10.1093/hmg/ddu478",

language = "英语",

volume = "24",

pages = "865--874",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "3",

}

Lu, X, Wang, L, Lin, X, Huang, J, Charles gu, C, He, M, Shen, H, He, J, Zhu, J, Li, H, Hixson, JE, Wu, T, Dai, J, Lu, L, Shen, C, Chen, S, He, L, Mo, Z, Hao, Y, Mo, X, Yang, X, Li, J, Cao, J, Chen, J, Fan, Z, Li, Y, Zhao, L, Li, H, Lu, F, Yao, C, Yu, L, Xu, L, Mu, J, Wu, X, Deng, Y, Hu, D, Zhang, W, Ji, X, Guo, D, Guo, Z, Zhou, Z, Yang, Z, Wang, R, Yang, J, Zhou, X, Yan, W, Sun, N, Gao, P & Gu, D 2015, 'Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension', Human Molecular Genetics, vol. 24, no. 3, pp. 865-874. https://doi.org/10.1093/hmg/ddu478

TY - JOUR

T1 - Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

AU - Lu, Xiangfeng

AU - Wang, Laiyuan

AU - Lin, Xu

AU - Huang, Jianfeng

AU - Charles gu, C.

AU - He, Meian

AU - Shen, Hongbing

AU - He, Jiang

AU - Zhu, Jingwen

AU - Li, Huaixing

AU - Hixson, James E.

AU - Wu, Tangchun

AU - Dai, Juncheng

AU - Lu, Ling

AU - Shen, Chong

AU - Chen, Shufeng

AU - He, Lin

AU - Mo, Zengnan

AU - Hao, Yongchen

AU - Mo, Xingbo

AU - Yang, Xueli

AU - Li, Jianxin

AU - Cao, Jie

AU - Chen, Jichun

AU - Fan, Zhongjie

AU - Li, Ying

AU - Zhao, Liancheng

AU - Li, Hongfan

AU - Lu, Fanghong

AU - Yao, Cailiang

AU - Yu, Lin

AU - Xu, Lihua

AU - Mu, Jianjun

AU - Wu, Xianping

AU - Deng, Ying

AU - Hu, Dongsheng

AU - Zhang, Weidong

AU - Ji, Xu

AU - Guo, Dongshuang

AU - Guo, Zhirong

AU - Zhou, Zhengyuan

AU - Yang, Zili

AU - Wang, Renping

AU - Yang, Jun

AU - Zhou, Xiaoyang

AU - Yan, Weili

AU - Sun, Ninglingh

AU - Gao, Pingjin

AU - Gu, Dongfeng

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84922421928

U2 - 10.1093/hmg/ddu478

DO - 10.1093/hmg/ddu478

M3 - 文章

C2 - 25249183

AN - SCOPUS:84922421928

SN - 0964-6906

VL - 24

SP - 865

EP - 874

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 3

ER -

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

Abstract

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