A systematic review of skin ageing genes reveals a pleiotropic landscape where skin colour genes and chromosomal band 16q24.3 genes may drive skin ageing

Skin ageing is the result of intrinsic genetic and extrinsic lifestyle factors. However, there is no consensus on skin ageing phenotypes and ways to quantify them. In this systematic review, we first carefully identified 56 skin ageing phenotypes from multiple literature sources and sought the best photo-numeric grading scales to evaluate them. Next, we conducted a systematic review on all 44 Genome-wide Association Studies (GWAS) on skin ageing published to date and identified genetic risk factors (2,349 SNPs and 366 genes) associated with skin ageing. We identified 19 promising SNPs found to be significantly (p-Value < 1E-05) associated with skin ageing phenotypes in two or more independent studies. Here we show, using enrichment analyses strategies and gene expression data, that 1) pleiotropy is a recurring theme among skin ageing genes, 2) SNPs associated with skin ageing phenotypes are mostly located in a small handful of 44 pleiotropic and hub genes (mostly on the chromosome band 16q24.3) and 32 skin colour genes, 3) genes traditionally identified to contribute to skin colour have more than just skin pigmentation roles, and 4) further progress towards understand the development of skin pigmentation requires understanding the contributions of genes on the chromosomal band 16q24.3. We anticipate our systematic review to serve as a hub to locate primary literature sources pertaining to the genetics of skin ageing and to be a starting point for more sophisticated work examining pleiotropic genes, hub genes, and skin ageing phenotypes.