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; Ningling Sun; Pingjin Gao; Dongfeng Gu

doi:10.1093/hmg/ddu478

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

Journal article

Open access

Peer reviewed

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, …

Human molecular genetics, Vol.24(3), pp.865-874

2015-02-01

DOI: https://doi.org/10.1093/hmg/ddu478

PMCID: PMC4303798

PMID: 25249183

Abstract

Adult

Aged

Asian Continental Ancestry Group - genetics

Blood Pressure - genetics

Calcium Channels, L-Type - genetics

Female

Genetic Loci

Genetic Predisposition to Disease

Genome-Wide Association Study - methods

Humans

Hypertension - genetics

Male

Mediator Complex - genetics

Middle Aged

Polymorphism, Single Nucleotide

Sodium-Bicarbonate Symporters - genetics

Steroid 21-Hydroxylase - genetics

China

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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.455 Genome-Wide Association Studies
Web Of Science research areas: Biochemistry & Molecular Biology; Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

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Title: Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension
Creators: Xiangfeng Lu - 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
Laiyuan Wang - State Key Laboratory of Cardiovascular Disease National Human Genome Center at Beijing, Beijing 100176, China
Xu Lin - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Jianfeng Huang - Hypertension Division Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
C Charles Gu - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA
Meian He - MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Hongbing Shen - Department of Epidemiology and Biostatistics, Ministry of Education Key Lab for Modern Toxicology School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Jiang He - Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA
Jingwen Zhu - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Huaixing Li - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
James E Hixson - Department of Epidemiology, University of Texas School of Public Health, Houston, TX 77025, USA
Tangchun Wu - MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Juncheng Dai - Department of Epidemiology and Biostatistics, Ministry of Education Key Lab for Modern Toxicology School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Ling Lu - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Chong Shen - Department of Epidemiology and Biostatistics, Ministry of Education Key Lab for Modern Toxicology School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
Shufeng Chen - 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
Lin He - Bio-X Institutes, Ministry of Education Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China
Zengnan Mo - Center for Genomic and Personalized Medicine, Medical Scientific Research Center and Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, China
Yongchen Hao - 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
Xingbo Mo - 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
Xueli Yang - 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
Jianxin Li - 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
Jie Cao - 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
Jichun Chen - 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
Zhongjie Fan - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
Ying Li - 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
Liancheng Zhao - 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
Hongfan Li - National Human Genome Center at Beijing, Beijing 100176, China
Fanghong Lu - Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Cailiang Yao - School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
Lin Yu - Department of Cardiology, Fujian Provincial People's Hospital, Fuzhou, Fujian 350004, China
Lihua Xu - Department of Cardiology, Affiliated Hospital of Beihua University, Beihua University, Jilin 132011, China
Jianjun Mu - Department of Cardiology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shannxi 710061, China
Xianping Wu - Center for Chronic and Noncommunicable Disease Control and Prevention, Sichuan Center of Disease Control and Prevention, Chengdu, Sichuan 610041, China
Ying Deng - Center for Chronic and Noncommunicable Disease Control and Prevention, Sichuan Center of Disease Control and Prevention, Chengdu, Sichuan 610041, China
Dongsheng Hu - School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China School of Medicine, Shenzhen University, Shenzhen, Guangdong 518000, China
Weidong Zhang - School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China
Xu Ji - Department of Internal Medicine, Xinle Red Cross Hospital, Xinle, Hebei 050700, China
Dongshuang Guo - Department of Internal Medicine, Yuxian Renmin Hospital, Yuxian, Shanxi 045100, China
Zhirong Guo - Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu 215123, China
Zhengyuan Zhou - Changshu Center of Disease Control and Prevention, Changshu, Jiangsu 215501, China
Zili Yang - Nantong Center of Disease Control and Prevention, Nantong, Jiangsu 226007, China
Renping Wang - Department of Internal Medicine, Shijiazhuang Greatwall Hospital, Shijiazhuang, Hebei 052260, China
Jun Yang - Department of Cardiology, Hanzhong People's Hospital, Hanzhong, Shannxi 723000, China
Xiaoyang Zhou - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
Weili Yan - Department of Clinical Epidemiology, Children's Hospital of Fudan University, Shanghai 200062, China
Ningling Sun - Department of Heart Center, Peking University People's Hospital, Beijing 100044, China and
Pingjin Gao - State Key Laboratory of Medical Genetics, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Dongfeng Gu - 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 gudongfeng@vip.sina.com
Publication Details: Human molecular genetics, Vol.24(3), pp.865-874
Grant note: D43 TW009107 / FIC NIH HHS U01HL072507 / NHLBI NIH HHS R01 HL087263 / NHLBI NIH HHS R01HL090682 / NHLBI NIH HHS R01HL087263 / NHLBI NIH HHS
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 25249183
PMCID: PMC4303798
Record Identifier: 991031619669602976