Genetic and phenotypic characterization of the iris pigmented collarette and its relationship with eye colour

Abstract The pigmented collarette or peripupillary ring is a visible anatomical feature of the human iris, yet its genetic basis and clinical relevance remain largely unexplored. In a cohort of 1,133 individuals, we investigated the relationships between eye colour, pigmented collarette presence, size and colour, iris surface features, benign melanocytic lesions, and 31 pigmentation-associated SNPs. As expected, strong associations were observed between eye colour and established pigmentation loci, particularly within HERC2 / OCA2 . Importantly, the heterozygous genotype of HERC2 rs12913832 was significantly associated with pigmented collarette presence, size and colour. Novel associations were identified between the SLC24A4 rs4900109 variant and pigmented collarette presence and size, independent of collarette colour, suggesting partially distinct genetic regulation of this trait. Additional pigmented collarette associations were observed for OCA2 , TYRP1 , ARFIP2 and an intergenic variant. Additionally, pigmented collarette presence was strongly associated with green irises and correlated with iris freckles, iris naevi and cutaneous naevi, indicating a link with generalized melanocytic activity. Several sex-specific genetic effects were also detected. These findings establish the pigmented collarette as a clinically relevant iris phenotype that is genetically related to overall eye colour but exhibiting trait-specific genetic associations, and may represent a visible marker of overall ocular and cutaneous pigmentation.