rs12913832

Genome-wide association study of sagging eyelids (dermatochalasis) in 5,578 Rotterdam Study participants and 1,053 TwinsUK twins identified a genome-wide significant protective effect for the C allele of rs11876749 (P=1.7×10⁻⁸) in a recessive model. Risk factors included age, male sex, lighter skin color, and higher BMI. Heritability of sagging eyelids was estimated at 61% in the twin cohort.

This genome-wide association study (GWAS) of pigmentary traits in East Asian populations (N=305 skin, N=342 iris) identifies a genome-wide significant signal for iris color in the OCA2 region, with rs1800414 (His615Arg) explaining 11.9%, 10.4%, and 6% of variation in b*, a*, and L* coordinates respectively. While no genome-wide significant signals were detected for skin pigmentation, rs2373391 in ZNF804B was replicated in independent Chinese samples (p=0.003).

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).

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.

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.

This study identified a founder mutation in HERC2 intron 86 (rs12913832) that is perfectly associated with blue eye color. Through linkage analysis of a large Danish family and association studies in 155 blue-eyed and 45 brown-eyed individuals, the researchers mapped the blue eye color locus to a 166 Kbp region and demonstrated that rs12913832 (G allele) and rs1129038 (A allele) are perfectly associated with blue eyes (P = 6.12e-46). Functional studies showed this regulatory element significantly reduces OCA2 promoter activity through differential binding of transcription factors.