Pathways Involved in Sasang Constitution from Genome-Wide Analysis in a Korean Population

Abstract

Sasang constitution (SC) medicine, a branch of Korean traditional medicine, classifies the individual into one of four constitutional types (Taeum, TE; Soeum, SE; Soyang, SY; and Taeyang, TY) based on physiologic characteristics. The authors of the current article recently reported individual genetic elements associated with SC types via genome-wide association (GWA) analysis. However, to understand the biologic mechanisms underlying constitution, a comprehensive approach that combines individual genetic effects was applied. Genotypes of 1222 subjects of defined constitution types were measured for 341,998 genetic loci across the entire genome. The biologic pathways associated with SC types were identified via GWA analysis using three different algorithms--namely, the Z-static method, a restandardized gene set assay, and a gene set enrichment assay. Distinct pathways were associated (p<0.05) with each constitution type. The TE type was significantly associated with cytoskeleton-related pathways. The SE type was significantly associated with cardio- and amino-acid metabolism-related pathways. The SY type was associated with enriched melanoma-related pathways. TY subjects were excluded because of the small size of that sample. Among these functionally related pathways, core-node genes regulating multiple pathways were identified. TJP1, PTK2, and SRC were selected as core-nodes for TE; RHOA, and MAOA/MAOB for SE; and GNAO1 for SY (p<0.05), respectively. The current authors systematically identified the biologic pathways and core-node genes associated with SC types from the GWA study; this information should provide insights regarding the molecular mechanisms inherent in constitutional pathophysiology.