Genome-wide association reveals pigmentation genes play a role in skin aging.
Green, Adèle C
MetadataShow full item record
AbstractLoss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies (GWAS) of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait (p = 4.1 × 10(-9)); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (p = 8.8 × 10(-13)), and rs4268748 near MC1R (p = 1.2 × 10(-15)). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinate of skin aging.
CitationGenome-wide association reveals pigmentation genes play a role in skin aging. 2017 J. Invest. Dermatol.
JournalThe Journal of Investigative Dermatology
- A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.
- Authors: Han J, Kraft P, Nan H, Guo Q, Chen C, Qureshi A, Hankinson SE, Hu FB, Duffy DL, Zhao ZZ, Martin NG, Montgomery GW, Hayward NK, Thomas G, Hoover RN, Chanock S, Hunter DJ
- Issue date: 2008 May 16
- A Genome-Wide Association Study Identifies the Skin Color Genes IRF4, MC1R, ASIP, and BNC2 Influencing Facial Pigmented Spots.
- Authors: Jacobs LC, Hamer MA, Gunn DA, Deelen J, Lall JS, van Heemst D, Uh HW, Hofman A, Uitterlinden AG, Griffiths CEM, Beekman M, Slagboom PE, Kayser M, Liu F, Nijsten T
- Issue date: 2015 Jul
- A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus.
- Authors: Han J, Qureshi AA, Nan H, Zhang J, Song Y, Guo Q, Hunter DJ
- Issue date: 2011 Mar 1
- Pigmentation-Independent Susceptibility Loci for Actinic Keratosis Highlighted by Compound Heterozygosity Analysis.
- Authors: Zhong K, Verkouteren JAC, Jacobs LC, Uitterlinden AG, Hofman A, Liu F, Nijsten T, Kayser M
- Issue date: 2017 Jan
- Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population.
- Authors: Peña-Chilet M, Blanquer-Maceiras M, Ibarrola-Villava M, Martinez-Cadenas C, Martin-Gonzalez M, Gomez-Fernandez C, Mayor M, Aviles JA, Lluch A, Ribas G
- Issue date: 2013 Mar 27