Novel Genes Affecting Blood Pressure Detected Via Gene-Based Association Analysis.
Novel Genes Affecting Blood Pressure Detected Via Gene-Based Association Analysis.
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通过基于基因的关联分析检测影响血压的新基因
DOI：
10.1534/g3.115.016915
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发表时间：
2015-03-26
期刊：
影响因子：
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通讯作者：
Zhang YH
中科院分区：
文献类型：
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作者：
Zhang H;Mo XB;Xu T;Bu XQ;Lei SF;Zhang YH
高血压是一种常见的疾病，也是心血管疾病的重要危险因素之一。这项研究的目的是确定更多的新的血压基因。基于对全基因组关联研究的荟萃分析的可用的基于SNP的P值，我们在总共69，395个个体中进行了基于基因的初始关联研究。为了找到支持所识别基因重要性的补充证据，我们进行了GRAIL（相关位点之间的基因关系）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和其他生物信息学分析。在基于基因的关联分析中，对人类基因组上大约22，129个基因进行了血压分析。Bonferroni校正后，共有43个基因具有统计学意义（P < 2.3×10−6）。从本研究的分析中获得的证据表明ID 1的重要性（P = 2.0×10−6），CYP 17 A1（P = 4.58×10−9），ATXN2（P = 1.07×10−13），CLCN 6（P = 4.79×10−9），弗林蛋白酶（P = 1.38×10−6）、HECTD 4（P = 3.95×10−11）、NPPA（P = 1.60×10−6）和PTPN 11（P = 8.89×10−10）在血压遗传基础中的作用。目前的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。
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.