Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2/OCA2 genotype and the IrisPlex model.

In recent years, several studies have greatly increased our understanding of the genetic basis underlying human eye colour variation. A large percentage of the eye colour diversity present in humans can already be genetically explained, so much so that different DNA-based eye colour prediction models, such as IrisPlex, have been recently developed for forensic purposes. Though these models are already highly accurate, they are by no means perfect, with many genotype-phenotype discrepancies still remaining unresolved. In this work we have genotyped six SNPs associated with eye colour (IrisPlex) in 535 individuals from Spain, a Mediterranean population. Aside from different SNP frequencies in Spain compared to Northern Europe, the results for eye colour prediction are quite similar to other studies. However, we have found an association between gender and eye colour prediction. When comparing similar eye colour genetic profiles, females tend, as a whole, to have darker eyes than males (and, conversely, males lighter than females). These results are also corroborated by the revision and meta-analysis of data from previously published eye colour genetic studies in several Caucasian populations, which significantly support the fact that males are more likely to have blue eyes than females, while females tend to show higher frequencies of green and brown eyes than males. This significant gender difference would suggest that there is an as yet unidentified gender-related factor contributing to human eye colour variation.