rs1800407

This global population study of 3,432 individuals from 73 populations examined 21 SNPs in the OCA2-HERC2 region associated with eye and skin pigmentation. Blue-eye associated haplotypes (BEH1, BEH2, BEH3) were found at high frequencies in Europe, with BEH2 showing the strongest signal of selection. The East Asian-specific missense SNP rs1800414 (His615Arg) was associated with lighter skin pigmentation and showed strong evidence of positive selection in East Asian populations.

Genetic association study of 202 melanoma patients examining SNPs in 24 candidate genes related to pigmentation and wound healing in relation to scar outcome. SNP rs8110090 in TGFβ1 was significantly associated with poorer scar outcomes (p=0.0002). Clinical factors including younger age, shorter time since surgery, and presence of infection or eczema were also associated with worse scarring.

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).

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.

This study examined genotype and haplotype frequencies of five SNPs in the OCA2 and HERC2 genes (rs7495174, rs4778241, rs4778138, rs12913832, rs1129038) that are associated with blue-brown eye color variation in a Japanese population of 523 brown-eyed individuals. Significant differences in genotype and haplotype distributions were found compared to African and European populations, with the A-GAG haplotype being most frequent in Japanese (0.568) versus low in Europeans (0.167), and rs12913832 and rs1129038 being mono-allelic in the Japanese population.

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.

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.