Research on the shared genetic structure of autoimmune diseases and psychiatric disorders based on genome structural equation modeling
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(x2=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.
NETL
NSTL
万方数据
