ArticleHuman genetics2008
Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression.
Article in Human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 4 of them syntheses that pooled it.
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Who cites it
136 citing papers in PubMed, 4 syntheses or guidelines pooled it, 348 citations in OpenAlex.
- Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations.BMC genetics · 2019Pooled it
- A Genome-Wide Association Study of Skin and Iris Pigmentation among Individuals of South Asian Ancestry.Genome biology and evolution · 2019Pooled it
- Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.Nature genetics · 2012Pooled it
- Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis.Pigment cell & melanoma research · 2010Pooled it
- Evolutionary Origin of Ocular Melanoma: Associations With rs12913832 G Allele Frequency and Latitude.Cancer medicine · 2026Observational
- 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.Scientific reports · 2026Article
- Multi-trait analysis of pigmentation traits in relation to skin and ocular cancers: Relevance for evolutionary medicine.Evolution, medicine, and public health · 2026Article
- Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology.Nature communications · 2025Article
- Why humans evolved blue eyes.Frontiers in psychology · 2025Article
- Modeling recent positive selection using identity-by-descent segments.American journal of human genetics · 2024Article
- Exploring Eye, Hair, and Skin Pigmentation in a Spanish Population: Insights from Hirisplex-S Predictions.Genes · 2024Article
- Functional analysis of two mutation sites in the OCA2 gene.Scientific reports · 2024Article
- The Chromatin Organization Close to SNP rs12913832, Involved in Eye Color Variation, Is Evolutionary Conserved in Vertebrates.International journal of molecular sciences · 2024Article
- Dense single nucleotide polymorphism testing revolutionizes scope and degree of certainty for source attribution in forensic investigations.Croatian medical journal · 2024Review
- Identification of Candidate Genes for Red-Eyed (Albinism) Domestic Guppies Using Genomic and Transcriptomic Analyses.International journal of molecular sciences · 2024Article
- Review
- Structural insights into pink-eyed dilution protein (Oca2).Bioscience reports · 2023Article
- Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan.Biomedicines · 2023Article
- Association between Variants in theGenes · 2023Article
- Identification of Polymorphisms in theThe journal of poultry science · 2023Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86 of HERC2. The brown eye color allele of rs12913832 is highly conserved throughout a number of species. As shown by a Luciferase assays in cell cultures, the element significantly reduces the activity of the OCA2 promoter and electrophoretic mobility shift assays demonstrate that the two alleles bind different subsets of nuclear extracts. One single haplotype, represented by six polymorphic SNPs covering half of the 3' end of the HERC2 gene, was found in 155 blue-eyed individuals from Denmark, and in 5 and 2 blue-eyed individuals from Turkey and Jordan, respectively. Hence, our data suggest a common founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color.
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