Association between Variants in the OCA2-HERC2 Region and Blue Eye Colour in HERC2 rs12913832 AA and AG Individuals

Genes (Basel). 2023 Mar 11;14(3):698. doi: 10.3390/genes14030698.


The OCA2-HERC2 region is strongly associated with human pigmentation, especially eye colour. The HERC2 SNP rs12913832 is currently the best-known predictor for blue and brown eye colour. However, in a previous study we found that 43 of 166 Norwegians with the brown eye colour genotype rs12913832:AA or AG, did not have the expected brown eye colour. In this study, we carried out massively parallel sequencing of a ~500 kbp HERC2-OCA2 region in 94 rs12913832:AA and AG Norwegians (43 blue-eyed and 51 brown-eyed) to search for novel blue eye colour variants. The new candidate variants were subsequently typed in a Norwegian biobank population (total n = 519) for population specific association analysis. We identified five new variants, rs74409036:A, rs78544415:T, rs72714116:T, rs191109490:C and rs551217952:C, to be the most promising candidates for explaining blue eye colour in individuals with the rs12913832:AA and AG genotype. Additionally, we confirmed the association of the missense variants rs74653330:T and rs121918166:T with blue eye colour, and observed lighter skin colour in rs74653330:T individuals. In total, 37 (86%) of the 43 blue-eyed rs12913832:AA and AG Norwegians could potentially be explained by these seven variants, and we suggest including them in future prediction models.

Keywords: DNA phenotyping; OCA2-HERC2; eye colour; forensic genetics; massively parallel sequencing; pigmentation.

MeSH terms

  • Eye
  • Eye Color* / genetics
  • Humans
  • Membrane Transport Proteins* / genetics
  • Norway
  • Ubiquitin-Protein Ligases / genetics


  • Membrane Transport Proteins
  • OCA2 protein, human
  • HERC2 protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Oculocutaneous albinism type 2

Grants and funding

This research received no external funding.