BMI-driven Clustering Multi-omics Analysis Profiles the Molecular Mechanism of Psycho-metabolic Nexus and Contributes to Risk Stratification

01_Z-score_corrected_for_N.R: Calculates sample-size-corrected Z-scores for BMI-associated SNVs across metabolic traits. 02_K-means_clustering.R: Performs missing-value imputation and K-means clustering to classify BMI-associated SNVs into five metabolic genetic clusters. 03_K-clustering_linear_regression_model.R: Tests the association patterns between SNV clusters and metabolic traits. 04_pPRS_Psy.R: Evaluates associations between cluster-specific pPRS and psychiatric phenotypes. 05_pPRS_Psy_Q1-Q4.R: Assesses psychiatric risk across quartiles of each cluster-specific pPRS. 06_pPRS_Psy_BMI.R: Tests whether BMI categories modify the associations between pPRS and psychiatric phenotypes. 07_BMI_SNV_Cluster_MR.R: Performs two-sample Mendelian randomization to evaluate directional effects of BMI-related genetic clusters on psychiatric traits. 08_GEMMA.sh: Runs GEMMA GWAS for each cluster-specific pPRS phenotype. 09_LDSC.sh: Performs LDSC genetic correlation analysis between GEMMA-derived pPRS GWAS results and psychiatric disorder GWAS summary statistics. 10_pPRS_Molecular.R: Tests associations between cluster-specific pPRS and molecular features such as proteins or metabolites. 11_Molecular_Psy.R: Evaluates associations between molecular features and psychiatric phenotypes. 12_WGCNA.R: Constructs WGCNA molecular co-expression modules using pPRS-associated proteins and metabolites. 13_WGCNA_Psy.R: Tests interactions between pPRS and WGCNA molecular modules on psychiatric phenotypes. 14_SEM.R: Builds a structural equation model to assess direct and indirect relationships among pPRS, molecular modules, and psychiatric disorders. 15_Mediation.R: Performs mediation analysis to identify molecular mediators linking pPRS to psychiatric phenotypes. GEMMA_GWAS_Summary.zip: GWAS summary statistics generated by GEMMA for the cluster-specific pPRS phenotypes.