1239 Genome-wide scans found variants in TERT associated with pigmented spots on hands/arms but not with other skin aging signs

Abstract

Skin aging is a health topic of growing concern to the general public. Researchers have been identifying extrinsic and intrinsic factors affecting skin aging. So far, genetic studies on skin aging have mainly focused on facial pigmentations and wrinkles. Here we are presenting the first genome-wide study on skin aging signs also including pigmentations and wrinkles on hands/arms (according to SCINEXATM). By sampling 2959 individuals from the Taizhou longitudinal cohort in China, we found pigmented spots on hands/arms strongly associated with genetics variants in TERT (p=1.51×10-28). This association was independently replicated in SALIA cohort in Germany. An associated haplotype near the TERT promoter region was identified by fine mapping. Luciferase reporter gene assay was perform to confirm that the haplotype is associated with modified expression level of TERT (P<0.01). We also showed that sun exposure is the main confounding factor that facial pigmented spots were not found to be associated with variants in TERT. Interestingly, even after controlling all the potential confounding factors, the variants are not associated with other skin aging signs, such as wrinkle and sagging, indicating that TERT is not affecting skin aging in a global aging mechanism, but rather affecting pigmented spots in a more specific yet unknown mechanism.