Anti-Irritant Strategy against Retinol Based on the Genetic Analysis of Korean Population: A Genetically Guided Top–Down Approach

Retinol, one of the most powerful cosmetic materials for anti-aging supported by a solid scientific background, exhibits a wide range of type and severity of irritation while showing limited user compliance. The lack of understanding of the mechanism of retinol-induced irritation has been the main hurdle in the development of anti-irritation strategies. Here, we identified 30 genetic markers related to the susceptibility to retinol-induced irritation in the Korean population. Based on the genetic analysis, a novel formula against retinol-induced irritation was developed, which mitigated the molecular pathogenesis—as indicated by the genetic markers—of the retinol-induced irritation. In human tests, this formula effectively decreased retinol-induced irritation. Furthermore, a polygenic risk score model for irritation was constructed and validated. Our comprehensive approach for the analysis of retinol-induced irritation will not only aid the development of anti-irritation strategies to ensure higher user compliance but also contribute to improving the current knowledge about the biological effects of retinoids.