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

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. 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. Hypertension Division Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA. MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. 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. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA. Department of Epidemiology, University of Texas School of Public Health, Houston, TX 77025, USA. Department of Epidemiology and Biostatistics, Ministry of Education Key Lab for Modern Toxicology School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Bio-X Institutes, Ministry of Education Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China. 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. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. National Human Genome Center at Beijing, Beijing 100176, China. Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China. School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Department of Cardiology, Fujian Provincial People's Hospital, Fuzhou, Fujian 350004, China. Department of Cardiology, Affiliated Hospital of Beihua University, Beihua University, Jilin 132011, China. Department of Cardiology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shannxi 710061, China. Center for Chronic and Noncommunicable Disease Control and Prevention, Sichuan Center of Disease Control and Prevention, Chengdu, Sichuan 610041, China. School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China School of Medicine, Shenzhen University, Shenzhen, Guangdong 518000, China. School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China. Department of Internal Medicine, Xinle Red Cross Hospital, Xinle, Hebei 050700, China. Department of Internal Medicine, Yuxian Renmin Hospital, Yuxian, Shanxi 045100, China. Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu 215123, China. Changshu Center of Disease Control and Prevention, Changshu, Jiangsu 215501, China. Nantong Center of Disease Control and Prevention, Nantong, Jiangsu 226007, China. Department of Internal Medicine, Shijiazhuang Greatwall Hospital, Shijiazhuang, Hebei 052260, China. Department of Cardiology, Hanzhong People's Hospital, Hanzhong, Shannxi 723000, China. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China. Department of Clinical Epidemiology, Children's Hospital of Fudan University, Shanghai 200062, China. Department of Heart Center, Peking University People's Hospital, Beijing 100044, China and. State Key Laboratory of Medical Genetics, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. 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.

Human molecular genetics. 2015;(3):865-74
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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.

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Publication Type : Meta-Analysis

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