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目的:采用全基因组外显子测序及生物信息学技术和方法，筛选强迫症致病基因，探讨强迫症潜在的发病机制。方法:获取5例首发强迫症患者和5例健康人外周血，提取DNA，进行全基因组外显子测序；检测病例组和对照组的全外显子中差异基因的相关位点，进行GO/Pathway/Disease富集分析；采用生物信息学技术进一步筛选与OCD相关的变异基因及其作用的信号通路。结果:(1)经高通量测序分析，OCD组与正常对照组对比发现共有262个差异突变基因(SNV＋INDEL)。(2)PLA2G4C基因的rs156631位点碱基(A/G)发生有义纯合突变，且与强迫症关联显著。(3)通过生物信息学技术分析，发现差异突变基因在磷脂酰胆碱GO条目(GO：0036151)、磷脂酶相关信号通路(ST_ID＝R-HSA-1482788)及神经精神疾病显著富集(n P<0.01)；检索KEGG数据库提示，PLA2G4C可通过影响磷脂代谢及炎症级联反应，参与强迫症的发病机制。n 结论:PLA2G4C基因的rs156631位点A/G纯合突变在强迫症发病中起重要作用。“,”Objective:To identify key genes by Whole Exome Sequencing (WES) and bioinformatics analysis in patients with obsessive compulsive disorder (OCD), as well as to explore the potential mechanism of OCD.Methods:DNA was extracted from the peripheral blood of 5 patients with first onset OCD and 5 normal subjects for WES.Relevant loci of genome-wide differentially expressed genes in the study group and the control group were detected and GO/Pathway/Disease enrichment analysis was performed.Bioinformatics techniques were used to further screen OCD-related mutated genes and potential signaling pathways.Results:(1) Through high-throughput sequencing analysis, 262 differentially mutated genes (SNV+ INDEL) were found in OCD group compared with normal control group.(2) The base (A/G) at rs156631 of PLA2G4C gene had A homozygous mutation and was significantly associated with OCD.(3) Bioinformation analysis showed that the differentially mutated genes showed significant enrichment in phosphatidylcholine GO entry (GO: 0036151), phospholipase related signaling pathway (ST_ID=R-HSA-1482788) and neuropsychiatric diseases (n P<0.01). A KEGG database search suggested that PLA2G4C may be involved in the pathogenesis of OCD by affecting phospholipid metabolism and inflammatory cascade.n Conclusion:Homozygous mutation at rs156631 A/G of PLA2G4C gene plays an important role in the pathogenesis of OCD.