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Skin Tanning Tied to 20 Genetic Loci in Large European GWAS

NEW YORK (GenomeWeb) – Researchers have uncovered 20 genetic loci that may explain why some people burn while others tan in response to sun exposure.

Whether or not someone can tan is determined by the ability of melanocytes to ramp up melanin production after exposure to ultraviolet radiation, and burning, rather than tanning, is a risk factor for developing skin cancer. In the US alone this year, about 91,270 new cases of melanoma are expected, according to the National Cancer Institute.

Using UK Biobank and other data, a King's College London-led team conducted a genome-wide association study in almost 180,000 individuals of European ancestry that identified 20 genomic loci, including 14 novel ones, that appear to be linked to the ability to tan. As they reported in Nature Communications today, five of the novel loci are in genes linked to the melanin synthesis pathway.

'This research is the largest genetic study to date of skin's tendency to tan or burn, and has doubled the number of genetic regions known to be involved in this feature," first author Alessia Visconti, a researcher in the Department of Twin Research and Genetic Epidemiology at King's College London, said in a statement.

For the discovery phase of their study, the researchers used data on 121,296 people of European descent from the UK Biobank who self-reported whether they never or rarely get tanned or whether they tanned easily. In their GWAS, the researchers uncovered 10,834 SNPs linked to tanning ability with genome-wide significance, which the researchers then traced to 30 distinct loci.

Twenty of those were then replicated in five additional cohorts of European ancestry, totaling 55,382 people.

Among the loci were six genes — including HERC2/ OCA2, IRF4, and MC1R — that had been previously linked to the ability to tan, as well as four genes that are linked to pigmentation. BNC2 was previously associated with skin pigmentation, the researchers noted, while TPCN2 was linked with hair color, and SLC24A4 and TYRP1 with both hair and eye color.

Ten of the associations were novel, and five of those genes — DCT, EMX2, PPARGC1B, PDE4B and RIPK5 — are involved in the synthesis of melanin. The other five don't have any obvious connection to tanning or pigmentation, the researchers said.

Eight of the loci the researchers linked to tanning ability have also been tied to skin cancer. For instance, variants in AGR3, MC1R, and TYR have been associated with cutaneous malignant melanoma, and variants in AHR, MC1R, and SLC45A2 have been linked to non-melanoma skin cancer.

Additionally, ATP11A — one of the novel loci the researchers found in this study — was associated with basal cell skin cancer in the first stage of a large GWAS, though the link couldn't be replicated in the final meta-analysis. Similarly, the researchers noted that there have been suggestive associations between TRPS1 — another of the novel associations — and skin cancer.

Visconti and her colleagues also examined the effects of these tanning ability-linked variants on hair color. MCR1, they noted, was more strongly associated with red hair than with tanning ability.

MCR1, which governs the proportion of eumelanin and phaeomelanin, is highly polymorphic among European populations. The researchers tested the association between nine MCR1 variants and tanning ability. All the variants, except R163Q and V92M, were significantly associated with ease of tanning. Seven of these variants, the researchers said, could fully explain their GWAS association at the MC1R locus.

"Our findings provide a set of genes that now need to be further explored to understand their contribution to increased risk of skin cancer," senior author Mario Falchi, also a researcher at King's College London, added.

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