The largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations, has identified 124 independent associations arising from 61 genomic regions, including 50 previously unidentified, and demonstrated that several of these genes also have an effect on eye color in Asians.
Human eye color is highly heritable, but its genetic architecture is not yet fully understood. Image credit: Pexels.
“Eye color is primarily determined by melanin abundance within the iris pigment epithelium, which is greater in brown than in blue eyes, and both the density and distribution of stromal melanocyte cells,” said co-senior author Dr. Pirro Hysi of King’s College London and colleagues.
“Ratios of the two forms of melanin, eumelanin and pheomelanin, within the iris as well as light absorption and scattering by extracellular components are additional factors that give irises their color. Absolute melanin quantity and the eumelanin/pheomelanin ratio are higher in brown irises, while blue or green irises have very little of both pigments and relatively more pheomelanin.”
“European populations, or those with partial European origin, display the largest diversity of iris color, varying from the lightest blue to darkest brown,” they added.
“The prevalence of blue eyes correlates with geographic latitude across Europe and neighboring areas, likely as a result of human migration, sexual, and possibly natural selection. Similarly, eye color variation with varying degrees of brown irises is seen in Asian populations, although with a much reduced range compared to brown eye color variation in Europeans.”
The study involved 157,485 individuals of European ancestry in the discovery stage and an additional 35,501 ancestral European individuals in the replication stage.
The authors identified 61 eye color genes, including 50 previously unidentified, and clearly demonstrated that eye color is a genetically highly complex human trait, similar to hair and skin color.
They found evidence for genes involved in melanin pigmentation, but they also found associations with genes involved in iris morphology and structure.
The further analysis in 1,636 Asian participants of Han Chinese and Indian ancestry suggests that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes.
“The findings are exciting because they bring us to a step closer to understanding the genes that cause one of the most striking features of the human faces, which has mystified generations throughout our history,” Dr. Hysi said.
“This will improve our understanding of many diseases that we know are associated with specific pigmentation levels.”
“This study delivers the genetic knowledge needed to improve eye color prediction from DNA as already applied in anthropological and forensic studies, but with limited accuracy for the non-brown and non-blue eye colors,” said co-senior author Dr. Manfred Kayser, a researcher at the Erasmus University Medical Center Rotterdam.
A paper on the findings was published in the journal Science Advances.
Mark Simcoe et al. 2021. Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color. Science Advances 7 (11): eabd1239; doi: 10.1126/sciadv.abd1239