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与自杀行为相关的基因本体论和通路的鉴定:全基因组关联研究的系统综述与富集分析

Identification of gene ontology and pathways implicated in suicide behavior: Systematic review and enrichment analysis of GWAS studies.

作者信息

González-Castro Thelma B, Tovilla-Zárate Carlos A, Genis-Mendoza Alma D, Juárez-Rojop Isela E, Nicolini Humberto, López-Narváez María L, Martínez-Magaña José J

机构信息

Multidisciplinary Academic Division of Jalpa de Méndez, Juárez Autonomous University of Tabasco, Jalpa de Méndez, Tabasco, Mexico.

Multidisciplinary Academic Division of Health Sciences, Juárez Autonomous University of Tabasco, Villahermosa, Tabasco, Mexico.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2019 Jul;180(5):320-329. doi: 10.1002/ajmg.b.32731. Epub 2019 May 2.

Abstract

Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to summarize and analyze the information obtained in SB GWAS, to explore the biological process gene ontology (GO) of genes associated with SB from GWAS, and to determine the possible implications of the genes associated with SB in Kyoto encyclopedias of genes and genomes (KEGG) biological pathways. The articles included in the analysis were obtained from PubMed and Scopus databases. Enrichment analyses were performed in Enrichr to evaluate the KEGG pathways and GO of the genes associated with SB of GWAS. The findings of biological process GO analysis showed 924 GO involved in genes related with SB; of those, the regulation of glucose import in response to insulin stimulus, regulation of protein localization to plasma membrane, positive regulation of endopeptidase activity, heterotypic cell-cell adhesion, regulation of cardiac muscle cell contraction, positive regulation of protein localization to plasma membrane, and positive regulation of protein localization to cell periphery biological process GO showed significant statistical association. Furthermore, we obtained 130 KEGG pathways involved in genes related with SB, which Aldosterone synthesis and secretion, Rap1 signaling pathway and arrhythmogenic right ventricular cardiomyopathy pathways showed a significant statistical association. These findings give a better perspective of the biological participation of genes associated with SB, which will be important to perform adequate strategies to prevent and treat SB.

摘要

已经开展了多项大规模研究,如全基因组关联研究(GWAS),以确定导致自杀行为(SB)的遗传因素。我们旨在总结和分析SB GWAS中获得的信息,探索GWAS中与SB相关基因的生物学过程基因本体论(GO),并确定与SB相关基因在京都基因与基因组百科全书(KEGG)生物学途径中的可能影响。分析中纳入的文章来自PubMed和Scopus数据库。在Enrichr中进行富集分析,以评估GWAS中与SB相关基因的KEGG途径和GO。生物学过程GO分析的结果显示,有924个GO参与了与SB相关的基因;其中,响应胰岛素刺激的葡萄糖导入调节、蛋白质定位于质膜的调节、内肽酶活性的正调节、异型细胞间粘附、心肌细胞收缩的调节、蛋白质定位于质膜的正调节以及蛋白质定位于细胞周边生物学过程GO显示出显著的统计学关联。此外,我们获得了130条与SB相关基因的KEGG途径,其中醛固酮合成和分泌、Rap1信号通路和致心律失常性右室心肌病途径显示出显著的统计学关联。这些发现为与SB相关基因的生物学参与提供了更好的视角,这对于实施预防和治疗SB的适当策略将具有重要意义。

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