Genome-wide association study of tanning phenotype in a population of European ancestry

Abstract

We conducted a multistage genome-wide association study (GWAS) of tanning response after exposure to sunlight in over 9,000 men and women of European ancestry who live in the United States. An initial analysis of 528,173 single-nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified LOC401937 (rs966321) on chromosome 1 as a novel locus highly associated with tanning ability, and we confirmed this association in 870 women controls from a skin cancer case-control study with joint P-value=1.6 x 10(-9). We further genotyped this SNP in two subsequent replication studies (one with 3,750 women and the other with 2,405 men). This association was not replicated in either of these two studies. We found that several SNPs reaching the genome-wide significance level are located in or adjacent to the loci previously known as pigmentation genes: MATP, IRF4, TYR, OCA2, and MC1R. Overall, these tanning ability-related loci are similar to the hair color-related loci previously reported in the GWAS of hair color.

Figure 1

Quantile-quantile plot of the -log₁₀ p-values from an analysis of the initial GWAS that did not adjust for principal components of genetic variation (black dots) and an analysis that did adjust for the four largest principal components (graydots). P-values smaller than 10⁻⁸ are not plotted.

Figure 2

−log10 p-values from the test of association with tanning response after exposure to UV in the initial GWAS, by position along chromosome. Only p-values smaller than 0.05 are plotted.