Green eyes remain rare in human populations due to specific genetic inheritance patterns
Specific genetic inheritance patterns and polygenic interactions—particularly at the OCA2-HERC2 locus—dictate the distribution and rarity of human eye colors.
The retrieved literature consistently supports the claim that human eye colors, including rare phenotypes, are governed by specific genetic inheritance patterns involving polygenic traits, epistasis, and variations within the HERC2-OCA2 region. None of the papers refute this foundational mechanism of pigmentation genetics.
Wojciech Branicki, Urszula Brudnik, Anna Wojas‐Pelc. Interactions Between <i>HERC2</i>, <i>OCA2</i> and <i>MC1R</i> May Influence Human Pigmentation Phenotype. 2009. https://doi.org/10.1111/j.1469-1809.2009.00504.x
Paper 0 confirms that human pigmentation and eye color are shaped by complex gene-gene interactions involving loci such as HERC2 and OCA2.
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J. Andersen, Carlotta Pietroni, P. Johansen, M. Andersen, V. Pereira, C. Børsting, N. Morling. Importance of nonsynonymous OCA2 variants in human eye color prediction. 2016. https://doi.org/10.1002/mgg3.213
Paper 1 notes that while the rs12913832 SNP strongly influences iris pigmentation, eye color determination cannot be fully explained without considering additional variants.
P. Suarez, Karine Baumer, D. Hall. Further insight into the global variability of the OCA2-HERC2 locus for human pigmentation from multiallelic markers. 2021. https://doi.org/10.1038/s41598-021-01940-w
Paper 2 demonstrates that specific haplotype structures across the OCA2-HERC2 locus account for the major proportion of human eye color variation.
C. Abbatangelo, Frida Lona Durazo, Melissa Edwards, Esteban J. Parra. A comparative GWAS of eye colour in light and dark eye genetic backgrounds defined by HERC2 rs12913832 polymorphism in a Canadian cohort of European ancestry. 2026. https://doi.org/10.1038/s41598-026-44580-8
Papers 7 and 8 highlight how polygenic inheritance patterns and specific gene-gene interactions modify primary genetic predictors to determine various eye color presentations.
C. Abbatangelo, Frida Lona Durazo, Melissa Edwards, Esteban J. Parra. A comparative GWAS of eye colour in light and dark eye genetic backgrounds defined by HERC2 rs12913832 polymorphism. 2025. https://doi.org/10.1101/2025.07.20.665796
Paper 11 explains that eye color is governed by polygenic inheritance exhibiting epistasis and incomplete dominance across multiple genes like HERC2 and OCA2.
Désirée White, Montserrat Rabago-Smith. Genotype-phenotype associations and human eye color.. 2011. https://doi.org/10.1038/jhg.2010.126
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