;How is "Facial Skin Youthfulness" encoded by the genome?
Do people say you look younger or older than your age? Why do some people look younger than their biological age? For many, the answer is skin. Skin is the interface between your insides and the outside environments, and failure to protect skin against sunlight can lead to visibly aged skin.
Studies have investigated genetic factors associated with skin age, rationalizing that failure to protect against sunlight or other skin issues will lead to visibly aged skin. These studies revealed a self-reported tanning association at the MC1R gene, regulating pigmentation. Other genes identified have been linked to several phenotypes, such as skin and hair pigmentation, poor tanning ability, and increased freckling. This apparent similarity in findings for objective and subjective measures of skin function is mirrored in studies where multiple measures of skin appearance and function are available in the same participants. Thus, it was predicted that subjective measures of perceived age might act as a proxy for underlying dermal integrity and sunlight exposure.
To test the hypothesis, researchers performed a genome-wide association study in 423,992 adult participants of UK Biobank by using questionnaire data on perceived age and genetic data imputed to the Haplotype Reference Consortium imputation panel. In the questionnaire, participants were asked to respond to the question, “Do people say that you look….?” The possible answers were “younger than you are,” “older than you are,” “about your age,” “do not know,” or “prefer not to answer.” Among participants, 8,630 reported looking older than their biological age, 103,300 reported looking about their age, and 312,062 reported looking younger than their biological age. There were trends with both age and sex, where females were more likely to report looking young for their age than males, and older participants were more likely to report looking young for their age than young participants. By comparing their answers to the questionnaire and genotype data, the study identified 74 novel and independent genetic loci associated with facial youthfulness. These loci include rs6996198 in the RP11-21C4.1 gene region, rs121908120 in the WNT10A gene, rs17036328 in the PPARG gene, rs4869723 in the AKAP12 gene, rs174548 in the FADS1 gene, and rs12878653 in the SYNE2 gene. Overall, common genetic variation was estimated to account for approximately 14% of the variation in perceived age, and the heritability of perceived age was partially shared with that of 75 other traits, including multiple traits representing adiposity. These results suggest that perceived age may be a useful proxy trait in genetic association studies.
One of the practical limitations was having people self-identify vs. previous approaches such as using a panel of volunteers to guess the age of a participant and compare that with actual age to generate a continuous measure. The statistical model showed that because of this there was a degree of misclassification that likely affected the statistical power— and led to some degree of underestimation. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/32339537/
Are you interested in learning more about your genetic tendency for facial skin youthfulness? You can login to your Genomelink TRAITS to see this new genetic trait.
