A GWAS identifies novel gene associations with facial skin wrinkling and mole count in Latin‐Americans

BACKGROUND Genome-wide association studies (GWAS) have identified genes influencing skin ageing and mole count in Europeans but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVE To conduct a GWAS for facial skin ageing and mole count in adults 6,000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's Omni Express chip. Association testing was performed on ~8,703,729 SNPs across the autosomal genome. RESULTS Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13.3 and 21q21.2), one with mole count (in 1q32.3), and one with both wrinkling and mole count (in 5p13.2). Associated SNPs in 5p13.2 and in 1p13 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32.3 are near the SLC30A1 gene, and those in 21q21.2 occur in a gene desert. Analysis of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.