rs1042602

This study examined associations between sun-sensitive pigmentary gene variants and serum PSA levels in 1033 older Australian men. Variants in SLC45A2 (rs28777: -19.6%, rs16891982: -17.3%) were associated with lower PSA levels in all men. Variants in MC1R (rs1805007) and ASIP (rs4911414) showed significant interactions with birth region, with higher PSA levels in ANZ-born men carrying the variants. Post-hoc analysis found increased testosterone in MC1R rs1805007 carriers and elevated dihydrotestosterone in ASIP rs1015362 carriers.

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.

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.

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 study evaluated the impact of population admixture on genetic association studies of type 2 diabetes and end-stage renal disease in African Americans using 70 ancestry informative markers (AIMs) genotyped in 577 cases and 596 controls. Eight T2DM candidate genes (TCF7L2, PPARG, CAPN10, KCNJ11, TCF1, HNF4A, ESR1, ENPP1) with 208 SNPs total were analyzed for association, with 47 SNPs (22.6%) nominally associated before admixture adjustment, but 9 of those (4% overall, 19% of associated SNPs) lost significance after adjusting for African ancestry. The admixture impact on association results was significantly correlated with absolute delta values (differences in allele frequencies between Yoruba and European populations) across dominant (r²=0.1997, P=0.0051), additive (r²=0.2662, P=0.0015), and recessive (r²=0.1735, P=0.0410) models.