Replication of acne susceptibility loci and gene-environment interactions with screen time in Singapore and Malaysia Chinese population.

Acne vulgaris is a common chronic inflammatory skin disorder with a substantial genetic contribution. However, replication of findings from genome-wide association studies across diverse populations remains limited. In this study, we evaluated 88 previously reported acne-associated variants in 2741 acne cases and 2235 controls from the Singapore/Malaysia Cross-sequential Genetic Epidemiology Study. Two association signals were replicated at Bonferroni-corrected significance: rs1159268 near TGFB2 at 1q41 and rs738409 in the PNPLA3 coding region at 22q13.31, with consistent directions of effect. Functional annotation and transcriptomic evidence supported the involvement of these loci in pathways related to pilosebaceous unit biology, including epithelial differentiation, tissue homeostasis, retinoid regulation, and lipid metabolism. Gene-environment interaction analyses further identified 12 variants whose associations with acne risk were modified by screen-time exposure. These findings suggest that screen-associated exposures may act as contextual modifiers of genetic susceptibility, potentially through lifestyle-related metabolic factors, circadian endocrine regulation, and oxidative stress responses. Together, these findings emphasize the importance of considering environmental exposures alongside genetic susceptibility to refine our understanding of acne pathogenesis.