Investigating the genetic architecture of eye colour in a Canadian cohort

Eye color is highly variable in populations with European ancestry, ranging from low to high quantities of melanin in the iris. Polymorphisms in the HERC2/OCA2 locus have the largest effect on eye color in these populations, although other genomic regions also influence eye color. We performed genome-wide association studies of eye color in a Canadian cohort of European ancestry (N = 5,641) and investigated candidate causal variants. We uncovered several candidate causal signals in the HERC2/OCA2 region, whereas other loci likely harbor a single causal signal. We observed colocalization of eye color signals with the expression or methylation profiles of cultured primary melanocytes. Genetic correlations of eye and hair color suggest high genome-wide pleiotropy, but locus-level differences in the genetic architecture of both traits. Overall, we provide a better picture of the polymorphisms underpinning eye color variation, which may be a consequence of specific molecular processes in the iris melanocytes.

Automated summary

Eye color varies greatly in populations with European ancestry, with the HERC2/OCA2 locus having the largest effect on eye color. Several candidate causal signals for eye color were identified, with colocalization with the expression or methylation profiles of melanocytes. Genetic correlations between eye and hair color suggest high genome-wide pleiotropy.