Objective: 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 physiological characteristics. We recently reported individual genetic elements associated with SC types via genome-wide association (GWA) analysis. However, to understand the biological mechanisms underlying constitution, a comprehensive approach that combines individual genetic effects should be applied.
Design: Genotypes of 1,222 subjects of defined constitution type were measured for 341,998 genetic loci across the entire genome. The biological pathways associated with SC types were identified via GWA analysis using three different algorithmsnamely, the Z-static method, restandardized gene set assay, and gene set enrichment assay.
Results: 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. Among these functionally related pathways, we identified core-node genes regulating multiple pathways. TJP1, PTK2, and SRC were selected as core-nodes for TE, RHOA and MAOA/MAOB for SE and GNAO1 for the SY type (p<0.05), respectively.
Conclusions: We systematically identified the biological pathways and core-node genes associated with SC types from the GWA study; this information should provide us with insights regarding the molecular mechanisms inherent to constitutional pathophysiology. |
