Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia; Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia; Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
J Invest Dermatol. 2024 Oct;144(10):2230-2239.e10. doi: 10.1016/j.jid.2024.02.019. Epub 2024 Mar 7.
Skin aging is a natural process that occurs over time but can be accelerated by sun exposure. Measuring skin age in a large population can provide insight into the extent of skin damage from sun exposure and skin cancer risk. Understanding the genetics of skin aging, within and across sexes (males and females), could improve our understanding of the genetic drivers of both skin aging and skin cancer. We used UK Biobank data to examine the genetic overlap between perceived youthfulness and traits relevant to actinic photoaging. Our GWAS identified 22 genome-wide significant loci for women and 43 for men. The genetic correlation (rg) between perceived youthfulness in men and women was significantly less than unity (rg = 0.75, 95% confidence interval = 0.69-0.80), suggesting a gene-by-sex interaction. In women, perceived youthfulness was modestly correlated with keratinocyte cancer (rg = -0.19) and skin tanning (rg = 0.18). In men, perceived youthfulness was correlated with male-pattern baldness (rg = -0.23). This suggests that the genetic architecture of perceived youthfulness may differ between sexes, with genes influencing skin tanning and skin cancer susceptibility driving the difference in women, whereas genes influencing male-pattern baldness and other puberty-related traits drive the difference in men. We recommend that future genetic analysis of skin aging include a sex-stratified component.
皮肤衰老属于自然过程，会随时间推移而发生，但日晒会加速其进程。对大量人群的皮肤年龄进行测量，有助于了解因日晒导致的皮肤损伤程度和皮肤癌风险。了解性别（男性和女性）内和性别间皮肤衰老的遗传基础，可增进我们对皮肤衰老和皮肤癌遗传驱动因素的理解。我们使用英国生物库数据，研究了人们对年轻度的感知与光老化相关特征之间的遗传重叠。我们的全基因组关联研究确定了 22 个与女性相关的全基因组显著位点和 43 个与男性相关的全基因组显著位点。男性和女性对年轻度的感知之间的遗传相关性（rg）显著低于 1（rg=0.75，95%置信区间=0.69-0.80），表明存在基因与性别的相互作用。在女性中，对年轻度的感知与角质形成细胞癌（rg=-0.19）和皮肤晒黑（rg=0.18）有一定的相关性。在男性中，对年轻度的感知与男性型秃发（rg=-0.23）相关。这表明，对年轻度的感知的遗传结构可能存在性别差异，在女性中，影响皮肤晒黑和皮肤癌易感性的基因导致了这种差异，而在男性中，影响男性型秃发和其他与青春期相关的特征的基因则导致了这种差异。我们建议，未来的皮肤衰老遗传分析应包括性别分层部分。
