Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans

Abstract

Aiming to identify novel genetic loci for pigmentation and skin cancer, we conducted a series of genome-wide association studies on hair color, eye color, number of sunburns, tanning ability and number of non-melanoma skin cancers (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European Americans in the replication stage (for eye color, 3871 males in the discovery stage and 2496 males in the replication stage). We targeted novel chromosome regions besides the known ones for replication. As a result, we identified a new region downstream of the EDNRB gene on 13q22 associated with hair color and the strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P = 2.4 × 10(-14); P = 5.4 × 10(-9) in the discovery set and P = 1.2 × 10(-6) in the replication set). Using blue, intermediate (including green) and brown eye colors as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3 associated with brown eye (P = 7.0 × 10(-8); P = 5.3 × 10(-5) in the discovery set and P = 0.02 in the replication set). Additionally, we identified a significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2 gene region on brown eye color (P-value for interaction = 3.8 × 10(-3)). As for the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on chromosome 14: rs12203592 in IRF4 (P = 7.2 × 10(-14); P = 1.8 × 10(-8) in the discovery set and P = 6.7 × 10(-7) in the replication set), rs12202284 between IRF4 and EXOC2 (P = 5.0 × 10(-8); P = 6.6 × 10(-7) in the discovery set and P = 3.0 × 10(-3) in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10(-8); P = 5.3 × 10(-7) in the discovery set and P = 0.01 in the replication set).

The Evolution of Tanning Needs Its Day in the Sun

“…Canonical pigmentation genes where variants are associated with differences in tanning capacity include WNT1 and SILV/Pmel17 (Paik et al 2011) in a Mongolian population and SLC45A2/MATP, IRF4, TYR, OCA2, HERC2, PPARGC1B, MITF and MC1R in broadly-collected European and European-American populations (Nan et al 2009;Shoag et al 2012;Zhang et al 2013). Additionally, these association studies identified variants in unexpected loci including GRM6 and ATF1 (Paik et al 2011) and LOC401937 (Nan et al 2009).…”

Génétique de la susceptibilité au cancer du sein — Polymorphismes et perspectives d’utilisation en clinique

“…While many of these studies focus on diseases such as cancer, susceptibility alleles for a host of various observable traits have been described. These range from height [6] and weight [7], hair color [8], and even to capacity to perform well in math [9].…”

Exploration of SNP variants affecting hair colour prediction in Europeans

“…Studies of the genetic basis of human pigmentation diversity indicate a high heritability and few genes playing a key role in determining hair colour [10][11][12][13]. Individual-specific differences are largely due to single-nucleotide polymorphisms (SNPs), with the largest proportion showing strong signals of association to human pigmentation variation from genome-wide association studies (GWAS) [14][15][16][17].…”