Genetic Analysis of Perceived Youthfulness Reveals Differences in How Men's and Women's Age Is Assessed

Nathan Ingold; Mathias Seviiri; Jue-Sheng Ong; Scott Gordon; Rachel E Neale; David C Whiteman; Catherine M Olsen; Stuart MacGregor; Matthew H Law

doi:10.1016/j.jid.2024.02.019

Genetic Analysis of Perceived Youthfulness Reveals Differences in How Men's and Women's Age Is Assessed

J Invest Dermatol. 2024 Mar 7:S0022-202X(24)00180-5. doi: 10.1016/j.jid.2024.02.019. Online ahead of print.

Authors

Nathan Ingold¹, Mathias Seviiri², Jue-Sheng Ong³, Scott Gordon⁴, Rachel E Neale⁵, David C Whiteman⁶, Catherine M Olsen⁵, Stuart MacGregor³, Matthew H Law²

Affiliations

¹ 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. Electronic address: nathan.ingold@qimrberghofer.edu.au.
² 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.
³ Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁴ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁵ Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Faculty of Medicine, The University of Queensland, Herston, Australia.
⁶ Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Public Health, University of Queensland, Herston, Australia.

PMID: 38460809
DOI: 10.1016/j.jid.2024.02.019

Abstract

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.

Keywords: Canadian Longitudinal Study of Aging (CLSA); Genetic correlation; Perceived youthfulness; QSkin Sun and health study; Sex-stratified GWAS.