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

ABSTRACT

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 rs12913832AA 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 rs12913832AA 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, rs74409036A, rs78544415T, rs72714116T, rs191109490C and rs551217952C, to be the most promising candidates for explaining blue eye colour in individuals with the rs12913832AA and AG genotype. Additionally, we confirmed the association of the missense variants rs74653330T and rs121918166T with blue eye colour, and observed lighter skin colour in rs74653330T individuals. In total, 37 (86%) of the 43 blue-eyed rs12913832AA and AG Norwegians could potentially be explained by these seven variants, and we suggest including them in future prediction models.