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 × 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.
authors.affiliation: 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.
authors.forename: Xiangfeng
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authors.affiliation: State Key Laboratory of Cardiovascular Disease National Human Genome Center at Beijing, Beijing 100176, China.
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authors.lastname: Wang
authors.affiliation: 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.
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authors.affiliation: Hypertension Division Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.affiliation: 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.
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authors.affiliation: 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.
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mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002681:China; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; C480067:MED13L protein, human; D056892:Mediator Complex; C422022:SLC4A7 protein, human; D027982:Sodium-Bicarbonate Symporters; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase