基于基因组结构方程模型的自身免疫性疾病和精神类疾病的共享遗传结构研究  

Research on the shared genetic structure of autoimmune diseases and psychiatric disorders based on genome structural equation modeling

作　　者：邓刘飞 薛舒婷 姚紫微 张潇迈 温艳超 刘龙 DENG Liu-fei;XUE Shu-ting;YAO Zi-wei;ZHANG Xiao-mai;WEN Yan-chao;LIU Long(Department of Health Statistics,School of Public Health,Shanxi Medical University,Taiyuan,Shanxi 030001,China;不详)

机构地区：[1]山西医科大学公共卫生学院卫生统计学教研室,山西太原030001 [2]山西医科大学医学科学院卫生统计教研室 [3]重大疾病风险评估山西省重点实验室,山西太原030001

出　　处：《现代预防医学》2025年第1期45-50,102,共7页Modern Preventive Medicine

摘　　要：目的 应用基因组结构方程模型(genome structural equation modeling,GSEM)和孟德尔随机化(Mendelian randomization, MR)研究六种自身免疫性疾病(autoimmune diseases,AID)和十种精神类疾病(psychiatric disorders,PD)之间的共享遗传结构。方法 本研究运用连锁不平衡分数回归评估疾病之间的遗传相关性;引入GSEM,在奇数染色体进行探索性因素分析、偶数染色体进行验证性因素分析来交叉验证,并结合路径分析建立三因子模型和层次模型。此外,对潜在因子(Factor)进行多变量全基因组关联研究,测试中介变量和Factor之间的双向因果关系。从而揭示各疾病之间复杂的遗传关系。结果 GSEM结果显示所选取的16种疾病可以被3个独立的因子所构成的三因子模型所解释,且在拟合研究数据时表现最佳(χ^(2)=865.291,AIC=929.291,CFI=0.940,SRMR=0.097),模型中,Factor1和Factor3均显示出与AID密切相关的特征;Factor2主要包含精神类疾病,硬皮病作为中介变量联系两类疾病;MR结果显示硬皮病和Factor2、Factor3之间存在双向因果效应。结论 GSEM和MR可以用于揭示AID和PD之间的共享遗传结构和因果效应,从而发现两者的相互作用,为理解复杂疾病之间的遗传关系提供了一个重要的方法学工具。Objective To investigate the shared genetic structure between six autoimmune diseases(AIDs)and ten psychiatric disorders(PDs)using Genome Structural Equation Modeling(GSEM)and Mendelian randomization(MR).Methods The research employed linkage disequilibrium score regression to assess the genetic correlations between diseases.GSEM was introduced for exploratory factor analysis on odd-numbered chromosomes and confirmatory factor analysis on even-numbered chromosomes for cross-validation,along with path analysis to establish a three-factor model and hierarchical model.Additionally,a multivariable genome-wide association study was conducted on latent factors to test the bidirectional causal relationships between mediating variables and factors,thereby revealing the complex genetic relationships among the diseases.Results GSEM results indicated that the selected 16 diseases could be explained by a three-factor model consisting of three independent factors,which fitted the research data best(χ^(2)=865.291,AIC=929.291,CFI=0.940,SRMR=0.097).In this model,Factor 1 and Factor 3 exhibited characteristics closely related to autoimmune diseases,while Factor 2 primarily encompassed psychiatric disorders,with scleroderma serving as a mediating variable linking the two types of diseases.MR results revealed a bidirectional causal effect between scleroderma and Factor 2 and Factor 3.Conclusion GSEM and MR can be utilized to uncover the shared genetic structure and causal effects between AIDs and PDs,thereby highlighting their interactions and providing an important methodological tool for understanding the genetic relationships among complex diseases.

关 键 词：基因组结构方程模型 因子分析 孟德尔随机化 自身免疫性疾病 精神类疾病 

分 类 号：R195[医药卫生—卫生统计学] R181.3[医药卫生—卫生事业管理]