Allergy and Molecular Immunology Laboratory, Lee Hiok Kwee Functional Genomics Laboratories, Department of Biological Sciences, Faculty of Science, National University of Singapore, Block S2, Level 5, 14 Science Drive 4, Lower Kent Ridge Road, Singapore, 117543, Singapore.
Sci Rep. 2022 Jul 30;12(1):13099. doi: 10.1038/s41598-022-17443-1.
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 (2349 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. Since numerous genes on the chromosome band 16q24.3 and skin colour genes show pleiotropy, we propose that (1) genes traditionally identified to contribute to skin colour have more than just skin pigmentation roles, and (2) 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.
皮肤老化是内在遗传和外在生活方式因素共同作用的结果。然而，目前对于皮肤老化表型及其量化方法尚无共识。在本系统综述中，我们首先仔细地从多个文献来源中确定了 56 种皮肤老化表型，并寻找了评估这些表型的最佳光电分级量表。接下来，我们对迄今为止发表的所有 44 项皮肤老化全基因组关联研究（GWAS）进行了系统综述，并确定了与皮肤老化相关的遗传风险因素（2349 个 SNP 和 366 个基因）。我们确定了 19 个有前途的 SNP，这些 SNP 在两项或更多独立研究中与皮肤老化表型显著相关（p 值 < 1E-05）。在这里，我们使用富集分析策略和基因表达数据表明：（1）多效性是皮肤老化基因的一个反复出现的主题；（2）与皮肤老化表型相关的 SNP 主要位于少数 44 个多效性和枢纽基因（主要位于 16q24.3 染色体带）和 32 个肤色基因中。由于 16q24.3 染色体带和肤色基因中的许多基因具有多效性，我们提出：（1）传统上被认为与肤色有关的基因不仅具有皮肤色素沉着作用；（2）进一步深入研究皮肤色素沉着的发展需要了解 16q24.3 染色体带基因的作用。我们预计本系统综述将成为查找与皮肤老化遗传学相关的原始文献的中心，并成为研究多效性基因、枢纽基因和皮肤老化表型的起点。
