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Mark James Simcoe, Manfred Kayser, Tim Spector, Christopher J Hammond, Pirro G Hysi; GWAS identifies 52 genomic regions associated with iris colour in a study conducted using almost 200,000 participants of European descent. Invest. Ophthalmol. Vis. Sci. 2018;59(9):781.
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© ARVO (1962-2015); The Authors (2016-present)
Iris colour is one of the most recognisable heritable human traits. It is also of clinical relevance as it may be related to conditions such as pigmentary glaucoma, cataract, and age-related macular degeneration. While a considerable portion of iris colour’s genetic aetiology was previously understood, there is still much to be explained. The purpose of this study was to identify genetic factors that explain the “missing heritability” of iris colour and provide a more complete understanding of this phenotype’s genetic architecture.
The discovery cohort for this study consisted of 157,485 unrelated research participants of European ancestry from the personal genetics company 23andMe, Inc. The phenotype was measured on a 7 point categorical scale ranging from light blue to dark brown, which was then transformed into a numerical scale for linear regression with adjustments made for age, sex, and population structure. Conditional analysis was then used to identify SNPs independently associated with iris colour. Replication was then conducted through meta-analysis of 41,990 European volunteers from 9 separate cohorts in the VisiGen consortium.
A total of 115 SNPs from within 52 separate genomic regions were independently associated with iris colour with genome-wide significance (p<5x10-8). The strongest associations were located within the oculocutaneous albinism 2 and HERC2 genes (p<1x10-300), but oculospanin (TSPAN10) (p=7.5x10-90), SOX5 (p=5.0x10-27), and several genes coding for members of the solute carrier family proteins were, among others, very significantly associated with iris colour. Predictive models incorporating this new information show a marked improvement compared to previously published ones.
Our study is the largest to have been conducted for testing genetic associations of iris colour. Though many of our newly identified loci possess small effect sizes, collectively they account for almost all of the phenotype’s genetic heritability, almost entirely explaining the heritability for blue eyes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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