Association between copy number variations in the OCA2-HERC2 locus and human eye colour

Human eye colour variation is strongly associated with single nucleotide polymorphisms (SNPs) in the OCA2-HERC2 locus, especially rs12913832 that is found in an enhancer element of OCA2. In a previous study we found that 43 out of 166 individuals in a Norwegian population with the brown eye colour genotype HERC2 rs12913832:AA or AG, did not have the expected brown eye colour. To investigate if duplications or deletions in the OCA2-HERC2 locus could explain the blue eye colour in these individuals, we analysed massively parallel sequencing (MPS) data for copy number variations (CNVs) in the OCA2-HERC2 region. The ∼500 kb long OCA2-HERC2 locus was sequenced in 94 individuals with the rs12913832:AG and AA genotypes. Of these, 43 were observed to have blue eye colour and 51 were observed to have brown eye colour. CNVs were analysed using R and the R-package panelcn.MOPS - CNV detection tool for targeted NGS panel data. In rs12913832:AG individuals, CNVs in 32 regions were significantly associated with blue eye colour (Benjamini-Hochberg adjusted p-value ≤ 0.05). In rs12913832:AA individuals, CNVs in 14 regions were associated with blue eye colour using raw p-values (p ≤ 0.05). The functional effects of these CNVs on OCA2 expression are yet to be investigated. However, this study suggests that CNVs in the OCA2-HERC2 locus might explain why some of the rs12913832:AG and AA individuals have unexpectedly blue eyes.