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.

中文翻译：

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对年轻感知的基因分析揭示了男性和女性年龄评估方式的差异

皮肤老化是随着时间的推移而发生的自然过程，但阳光照射会加速皮肤老化。测量大量人群的皮肤年龄可以深入了解阳光照射造成的皮肤损伤程度和皮肤癌风险。了解不同性别（男性和女性）皮肤衰老的遗传学，可以提高我们对皮肤衰老和皮肤癌遗传驱动因素的理解。我们使用英国生物银行的数据来检查感知的年轻性和与光化光老化相关的特征之间的遗传重叠。我们的 GWAS 确定了女性 22 个全基因组重要位点和男性 43 个位点。男性和女性感知的年轻度之间的遗传相关性 (rg) 显着低于统一性（rg = 0.75，95% 置信区间 = 0.69–0.80），表明基因与性别之间存在相互作用。在女性中，青春感与角质形成细胞癌（rg = -0.19）和皮肤晒黑（rg = 0.18）有一定的相关性。在男性中，感知的年轻与男性型秃发相关（rg = -0.23）。这表明，感知年轻的基因结构可能因性别而异，影响皮肤晒黑和皮肤癌易感性的基因驱动了女性的差异，而影响男性型秃发和其他青春期相关特征的基因驱动了男性的差异。我们建议未来对皮肤老化的遗传分析包括性别分层成分。