3对不同抑郁表型青少年同卵双生子的差异甲基化研究  

Methylation differences in 3 pairs of identical twin adolescents with different depressive phenotypes

作　　者：易立 侯枭[2] 杨舒 赵连生[3] 陈晓鹭 邓伟 陈界衡 唐伟杰 张书弟 傅一笑[1] YLi;HOU Xiao;YANG Shu;ZHAO Liansheng;CHEN Xiaolu;DENG Wei;CHEN Jieheng;TANG Weijie;ZHANG Shudi;FU Yixiao(Department of Psychiatry,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400016;Department of Clinical Medicine,Chongqing Medical and Pharmaceutical College,Chongqing,401331;Mental Health Center,Department of Psychiatric Medicine,West China Hospital of Sichuan University,Chengdu,Sichuan Province,610041;Physiotherapy Center,Hangzhou Seventh People's Hospital,Hangzhou,Zhejiang Province,310000,China)

机构地区：[1]重庆医科大学附属第一医院精神科,重庆400016 [2]重庆医药高等专科学校临床医学院,重庆401331 [3]四川大学华西医院精神医学研究室心理卫生中心,成都610041 [4]杭州市第七人民医院物理诊疗中心,杭州310000

出　　处：《陆军军医大学学报》2022年第4期302-309,共8页Journal of Army Medical University

基　　金：重庆市基础科学与前沿技术研究项目(cstc2018jcyjAX0252);重庆市卫生和计划生育委员会与重庆市科学技术委员会联合项目(2019MSXM045)。

摘　　要：目的对同卵不同抑郁表型双生子外周血DNA甲基化差异进行筛查,探讨差异基因是否可作为参与抑郁发生的候选基因。方法募集在校青少年双生子并进行卵形鉴定。以贝克抑郁量表第2版(Beck Depression Inventory-Ⅱ,BDI-Ⅱ)、长处与困难问卷(Strengths and Difficulties Questionnaire,SDQ)学生版本的情绪因子得分确定双生子个体间的抑郁表型差异。850k甲基化测序后选取P<0.05、且甲基化β值差值绝对值大于0.1(|Δβ|>0.1)为差异甲基化位点。进行基因本体论(GO)功能注释分析和京都基因和基因组百科全书(KEGG)通路富集分析,以及蛋白质-蛋白质相互作用(PPI)网络,以识别与抑郁症(major depressive disorder,MDD)相关的重要基因及其甲基化水平改变。结果纳入同卵不同抑郁表型青少年双生子3对,分为抑郁表型组和正常表型组,两组间共筛选出57个有甲基化水平差异基因,其中45个基因DNA甲基化水平升高,12个基因DNA甲基化水平降低。GO分析显示差异基因在中枢神经系统发育、RNA代谢过程调控等生物学过程富集显著,KEGG分析发现其在突触长时程抑制(LTD)、PI3K-Akt信号通路、TNF信号通路有明显富集。而在PPI网络中发现RHOA与多个差异甲基化基因存在直接或间接相互作用。结论在同卵不同抑郁表型双生子外周血中存在CSF1R、NOS1、AHR等基因的DNA甲基化水平改变,可能调节基因表达并通过LTD、PI3K-Akt等信号通路参与抑郁发生。Objective To investigate the differences of peripheral blood DNA methylation in identical twin adolescents with different depressive phenotypes and explore whether these differentially expressed genes can be used as candidate genes involved in the occurrence of depression. Methods Three pairs of verified identical twin adolescents( 12 ~ 18 years old) were recruited in this study. Phenotypic differences of depression between the twins were determined by Beck Depression Inventory-Ⅱ( BDI-Ⅱ) scores and emotional factor scores of Strength and Difficulty Questionnaire( SDQ) for students. After Infinium MethylationEPIC BeadChip Kit was used to interrogate over 850 k methylation sites,those with P<0.05 and the absolute value difference of methylation β value greater than 0. 1( |△β| > 0. 1) were selected as the differential methylation sites. Gene Ontology( GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis,as well as protein-protein interaction( PPI)network were performed to identify important genes associated with major depressive disorder( MDD) and their methylation changes. Results Three pairs of identical twin adolescents with different depressive phenotypes were divided into depressive phenotype group and normal phenotype group. A total of 57 genes with different methylation levels were screened between the 2 groups,including 45 genes with increased and 12 genes with decreased DNA methylation levels. GO analysis showed that differential genes were most significantly enriched in biological processes such as central nervous system development and regulation of RNA metabolic process.KEGG analysis indicated that differential genes were significantly enriched in synaptic long-term depression( LTD),PI3 K-Akt signaling pathway and TNF signaling pathway. Besides,direct or indirect interactions between RHOA and several differential methylated genes were found in PPI network. Conclusion Changes in DNA methylation levels of CSF1 R,NOS1,AHR and other genes i

关 键 词：DNA甲基化 抑郁 双生子 青少年 

分 类 号：R394.1[医药卫生—医学遗传学] R446.119[医药卫生—基础医学]