Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

摘要

European ancestry individuals provided the matrix of genetic covariances and orthogonal transformation coefficients. The four chronic musculoskeletal pain phenotypes were decomposed into four GIPs. Orthogonal transformation coefficients were further used to construct GIPs in the replication cohorts of European, African, and South Asian ancestry individuals. For each GIP, GWAS results were obtained. Replication of associations and in silico functional analyses were based on the meta-analyses of GWAS for the replication cohorts and European ancestry cohorts, respectively. For replicated loci, the most likely causal genes were prioritized. DEPICT Data-driven Expression Prioritized Integration for Complex Traits framework, GIP genetically independent phenotype, PC principal components, SMR/HEIDI Summary data-based Mendelian Randomization analysis followed by the Heterogeneity in Dependent Instruments test, FUMA Functional Mapping and Annotation of Genome-Wide Association Studies platform.