摘要：SummaryEye color is highly variable in populations with European ancestry, ranging from low to high quantities of melanin in the iris. Polymorphisms in theHERC2/OCA2locus 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 theHERC2/OCA2region, 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.Graphical abstractDisplay OmittedHighlights•Genome-wide association studies of eye color in 5,641 participants•Multiple independent candidate causal variants were identified acrossHERC2/OCA2•Single candidate causal variants observed on or nearIRF4, SLC24A4, TYR,andTYRP1•Colocalization of eye color signals with expression and methylation profilesGenetics; Genomics; Human Genetics
