【摘要】 目的 识别介导儿童期经历中等至极端虐待与抑郁障碍相关的甲基化基因，有助于在基因水平上阐明抑郁障碍的发病机制，同时也可为抑郁障碍的临床治疗提供靶点。方法 本研究将经典主成分分析、去稀疏化LASSO、柯西P-value整合有机地结合起来识别具有中介效应的甲基化基因。数据来源于Gene Expression Omnibus(GEO)数据库，分析采用基于R 4.2.2的高维推断(hdi)包进行分析。结果 采用主成分分析提取基因区域信息，可获得18203个基因。通过构建的高维中介效应模型对该基因数据进行分析，识别出具有潜在中介效应的1个甲基化基因，即基因ELAC1。结论 采用整合的中介效应模型识别出甲基化基因ELAC1,该基因在人脑中有较高的表达，可能与人类精神疾病相关，故该甲基化基因很可能介导了儿童期经历中等至极端虐待后导致成年抑郁障碍的发生。更多还原

【Abstract】 Objective The study is aimed at identifying the methylation genes that can mediate from childhood maltreatment to depression and can also provide a target for clinical treatment of depression. Methods The classical principal component analysis, de-sparsified LASSO, and Cauchy P-value combination were integrated to identify methylated genes with mediating effects. The data were downloaded from Gene Expression Omnibus(GEO)database, and the analysis was carried out with high-dimensional inference(hdi)package based on R4.2.2. Results The principal component analysis was used to extract gene information, and 18203 genes could be obtained from sites data. The integrated model was used to do the mediation analysis, and a methylated gene with a potential mediation effect was identified, namely the gene ELAC1. Conclusion The integrated mediation effect model identified the methylated gene ELAC1, which is highly expressed in the human brain and may be associated with human psychiatric disorders. Therefore, the methylated gene is likely to mediate the occurrence of adult depression after childhood maltreatment.更多还原