541 Gene set enrichment analysis identifies biological networks associated with skin aging in a large Japanese population: Data from the Nagahama cohort

Skin aging is driven by both intrinsic and extrinsic factors, such as chronic UV exposure, pollution and smoking. We conducted a genome wide association study (GWAS) on 1049 Japanese women from the Nagahama cohort and identified new biological mechanisms of four major outcomes in skin aging, namely photoaging, solar lentigines, wrinkles, and sagging. Gene Set Enrichment Analysis using KEGG database was applied on the genetic data. The significance of the associations was assessed using the False Discovery Rate (FDR). Only one pathway, the “Huntington’s disease pathway”, reached the 0.05 FDR threshold. This pathway was associated with the wrinkle phenotype. Among the four outcomes, fifteen reached also the FDR 0.25, such as “melanogenesis” pathway for the lentigines. This analysis highlighted also relevant pathways with a nominal p-value below 0.05 that we already highlighted in Caucasian population GWAS study such as “Arginine and Proline metabolism pathway” for lentigines or “mTOR signaling pathway” for sagging that tends to be also significant for wrinkle pathway. Overall, our results suggest that some biological mechanisms are common for skin aging outcomes such as “mTOR pathway”, a well-known aged-associated mechanism but specific pathways were also identified for each skin aging sign. These data contribute to our knowledge of skin aging in Japanese population.