rs26722

This study demonstrates that human hair color can be predicted from DNA variants with high accuracy using a multinomial logistic regression model. A subset of 13 genetic markers from 11 genes (MC1R, HERC2, IRF4, TYR, EXOC2, SLC45A2, TYRP1, OCA2, SLC24A4, KITLG, ASIP) predicted hair color categories in Polish Europeans with AUC values of 0.93 for red hair, 0.87 for black hair, 0.82 for brown hair, and 0.81 for blond hair. MC1R variants showed the strongest association with red hair (OR=12.64 for R variants, P=2.5×10⁻¹⁷), while rs12913832 in HERC2 was significantly associated with darker hair colors (OR=3.33 for black, P=4.3×10⁻⁶).

Genome-wide association studies and comparative genomics have identified major pigmentation loci (SLC24A5, SLC45A2, TYR, OCA2, MC1R, IRF4, TPCN2) showing evidence of strong natural selection in human populations. Light skin variants in Europeans and Asians underwent complete or near-complete selective sweeps, with SLC24A5 rs1426654 and SLC45A2 variants representing independent evolutionary mechanisms. Critical skin-lightening variants arose 11,000-30,000 years ago during human demographic expansion, driven by UV radiation exposure, vitamin D synthesis requirements, and possibly sexual selection.

Nested case-control study of 1,673 Caucasian women examining 15 SNPs in pigmentation genes. TYR Arg402Gln (rs1126809) and SLC45A2 Phe374Leu (rs16891982) were significantly associated with skin color and tanning ability. ASIP haplotype (rs4911414[T], rs1015362[G]) increased melanoma risk (OR 1.68) and SCC risk (OR 1.54), while TYRP1 rs1408799 and SLC45A2 -1721 C>G (rs13289) showed protective effects against melanoma (OR 0.77, 0.75 respectively). No associations remained significant after Bonferroni correction.

A cross-sectional genetic association study examining 362 Danish individuals investigating relationships between pigmentation genes and quantitative skin color, nevus counts, and familial atypical multiple-mole and melanoma (FAMMM) syndrome. MC1R variants were significantly associated with lighter arm pigmentation (p < 0.001), indicating effects on tanning response rather than constitutive skin color. No significant associations with FAMMM or nevus counts remained significant after Bonferroni correction for multiple testing.

A Spanish case-control study (131 melanoma patients, 245 controls) investigated 23 SNPs in six pigmentation genes (ASP, OCA2, TYR, TYRP1, SILV, SLC45A2) for melanoma susceptibility. The variant allele of SLC45A2 c.1122C>G (p.Phe374Leu, rs16891982) was associated with protection from melanoma (OR 0.41, 95% CI 0.24-0.70, adjusted P=0.008), validated by associations with dark hair, skin, and eye color.

This Danish study of 246 healthy individuals and 116 at-risk melanoma patients investigated associations between 32 pigmentary SNPs and quantitative skin color, nevi count, and familial atypical multiple-mole and melanoma (FAMMM) syndrome. Individuals carrying two or more MC1R variants (including missense mutations p.TYR152* and frameshift p.Asn29Glnfs*14) had significantly lighter skin on the upper-inner arm (p<0.001) reflecting impaired tanning ability, but no associations were found with FAMMM syndrome, suggesting FAMMM genetics are distinct from pigmentation pathways.

This study investigates allele frequencies of two coding SNPs in pigmentation genes SLC24A5 (p.A111T, rs1426654) and SLC45A2 (p.L374F, rs16891982) across multiple human populations including Chinese, Uygurs, Ghanaians, South African Xhosa, South African Europeans, and Sri Lankans. The derived 111T allele of SLC24A5 and 374F allele of SLC45A2 are nearly fixed in Europeans but absent or rare in other populations, confirming their utility as ancestry informative markers (AIMs). The study demonstrates that SLC45A2 is a more specific AIM than SLC24A5, particularly for distinguishing Sri Lankans from Europeans, and provides evidence for directional selection acting on these genes in European populations.

This study examined two SNPs in the MATP gene (SLC45A2) for associations with natural human pigmentation variation in 608 individuals across four populations. In Caucasians, the 374Leu and 272Lys alleles showed strong associations with darker pigmentation, with odds ratios of 25.63-43.23 for black hair and 8.27-28.65 for olive skin, representing the first significant report of MATP polymorphisms affecting normal pigmentation variation.