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通过基于基因的关联分析检测到的影响血压的新基因

Novel Genes Affecting Blood Pressure Detected Via Gene-Based Association Analysis.

作者信息

Zhang Huan, Mo Xing-Bo, Xu Tan, Bu Xiao-Qing, Lei Shu-Feng, Zhang Yong-Hong

机构信息

Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, People's Republic of China.

Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, People's Republic of China Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.

出版信息

G3 (Bethesda). 2015 Mar 26;5(6):1035-42. doi: 10.1534/g3.115.016915.

Abstract

Hypertension is a common disorder and one of the most important risk factors for cardiovascular diseases. The aim of this study was to identify more novel genes for blood pressure. Based on the publically available SNP-based P values of a meta-analysis of genome-wide association studies, we performed an initial gene-based association study in a total of 69,395 individuals. To find supplementary evidence to support the importance of the identified genes, we performed GRAIL (gene relationships among implicated loci) analysis, protein-protein interaction analysis, functional annotation clustering analysis, coronary artery disease association analysis, and other bioinformatics analyses. Approximately 22,129 genes on the human genome were analyzed for blood pressure in gene-based association analysis. A total of 43 genes were statistically significant after Bonferroni correction (P < 2.3×10(-6)). The evidence obtained from the analyses of this study suggested the importance of ID1 (P = 2.0×10(-6)), CYP17A1 (P = 4.58×10(-9)), ATXN2 (P = 1.07×10(-13)), CLCN6 (P = 4.79×10(-9)), FURIN (P = 1.38×10(-6)), HECTD4 (P = 3.95×10(-11)), NPPA (P = 1.60×10(-6)), and PTPN11 (P = 8.89×10(-10)) in the genetic basis of blood pressure. The present study found some important genes associated with blood pressure, which might provide insights into the genetic architecture of hypertension.

摘要

高血压是一种常见疾病,也是心血管疾病最重要的危险因素之一。本研究的目的是识别更多与血压相关的新基因。基于全基因组关联研究荟萃分析中公开可用的基于单核苷酸多态性(SNP)的P值,我们在总共69395名个体中进行了初步的基于基因的关联研究。为了找到补充证据来支持所识别基因的重要性,我们进行了GRAIL(相关基因座之间的基因关系)分析、蛋白质-蛋白质相互作用分析、功能注释聚类分析、冠状动脉疾病关联分析以及其他生物信息学分析。在基于基因的关联分析中,对人类基因组上约22129个基因进行了血压分析。经过Bonferroni校正后,共有43个基因具有统计学意义(P < 2.3×10⁻⁶)。本研究分析获得的证据表明,ID1(P = 2.0×10⁻⁶)、CYP17A1(P = 4.58×10⁻⁹)、ATXN2(P = 1.07×10⁻¹³)、CLCN6(P = 4.79×10⁻⁹)、FURIN(P = 1.38×10⁻⁶)、HECTD4(P = 3.95×10⁻¹¹)、NPPA(P = 1.60×10⁻⁶)和PTPN11(P = 8.89×10⁻¹⁰)在血压的遗传基础中具有重要意义。本研究发现了一些与血压相关的重要基因,这可能为高血压的遗传结构提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f92/4478534/a04f118ef931/1035f1.jpg

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