ArticleAmerican journal of human genetics2008
A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color.
Article in American journal of human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 4 of them syntheses that pooled it.
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Who cites it
167 citing papers in PubMed, 4 syntheses or guidelines pooled it, 384 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
- 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
- Association between a germline OCA2 polymorphism at chromosome 15q13.1 and estrogen receptor-negative breast cancer survival.Journal of the National Cancer Institute · 2010Pooled it
- Genome-wide association study identifies a genetic variant associated with risk for more aggressive prostate cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2011Trial
- Article
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- Haplotype-Based Analysis of OCA2 Variants in Oculocutaneous Albinism.Pigment cell & melanoma research · 2026Article
- 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
- Global patterns of natural selection inferred using ancient DNA.bioRxiv : the preprint server for biology · 2026Article
- Genetics of Skin, Hair, and Eye Color in Human Pigmentation Disorders.Annals of human genetics · 2025Review
- Mendelian genetics and eugenics.American journal of human genetics · 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
- Genetic diversity and signatures of selection in Icelandic horses and Exmoor ponies.BMC genomics · 2024Article
- Genotype-Phenotype Correlation Model for the Spectrum ofDiagnostics (Basel, Switzerland) · 2024Article
- Predictive accuracy of genetic variants for eye color in a Kazakh population using the IrisPlex system.BMC research notes · 2024Article
- The Chromatin Organization Close to SNP rs12913832, Involved in Eye Color Variation, Is Evolutionary Conserved in Vertebrates.International journal of molecular sciences · 2024Article
- Identification of Candidate Genes for Red-Eyed (Albinism) Domestic Guppies Using Genomic and Transcriptomic Analyses.International journal of molecular sciences · 2024Article
107 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
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Abstract
We have previously demonstrated that haplotypes of three single nucleotide polymorphisms (SNPs) within the first intron of the OCA2 gene are extremely strongly associated with variation in human eye color. In the present work, we describe additional fine association mapping of eye color SNPs in the intergenic region upstream of OCA2 and within the neighboring HERC2 (hect domain and RLD2) gene. We screened an additional 92 SNPs in 300-3000 European individuals and found that a single SNP in intron 86 of HERC2, rs12913832, predicted eye color significantly better (ordinal logistic regression R(2) = 0.68, association LOD = 444) than our previous best OCA2 haplotype. Comparison of sequence alignments of multiple species showed that this SNP lies in the center of a short highly conserved sequence and that the blue-eye-associated allele (frequency 78%) breaks up this conserved sequence, part of which forms a consensus binding site for the helicase-like transcription factor (HLTF). We were also able to demonstrate the OCA2 R419Q, rs1800407, coding SNP acts as a penetrance modifier of this new HERC2 SNP for eye color, and somewhat independently, of melanoma risk. We conclude that the conserved region around rs12913832 represents a regulatory region controlling constitutive expression of OCA2 and that the C allele at rs12913832 leads to decreased expression of OCA2, particularly within iris melanocytes, which we postulate to be the ultimate cause of blue eye color.
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