Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci
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Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information. Here, we quantified continuous eye color variation into hue and saturation values using high-resolution digital full-eye photographs and conducted a genome-wide association study on 5,951 Dutch Europeans from the Rotterdam Study. Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association. The latter two loci were replicated in 2,261 individuals from the UK and in 1,282 from Australia. The LYST gene at 1q42.3 and the DSCR9 gene at 21q22.13 serve as promising functional candidates. A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits.
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The eye color locus was later refined to a small region 50 kb upstream of OCA2 in an intron of the HERC2 gene.
“This eye color locus was later refined to a small region 50 kb upstream of OCA2 in an intron of the HERC2 gene [7], [8], [10].”
From Genetic Architecture of Skin and Eye Color in an African-European Admixed Population (2013) · cites this paper as [8]
Liu et al. (2010) found that rs12913832 has the strongest effect when eye color is measured quantitatively and can explain most of the variance in eye color amongst Europeans.
“A recent study by Liu et al. (2010) found that rs12913832 has the strongest effect when eye color is measured quantitatively and can explain most of the variance in eye color amongst Europeans.”
From A global view of the OCA2-HERC2 region and pigmentation (2012) · cites this paper as Liu et al. (2010)
Liu et al. report that quantitation improved the power to detect association signals at some known pigmentation genes and facilitated the identification of two novel replicated eye color loci at 17q25 and 21q22.
“These authors report that the quantitation improved the power to detect the association signals at some known pigmentation genes and also facilitated the identification of two novel replicated eye color loci at 17q25 and 21q22.”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [11]
Other eye color loci reported have been estimated each to explain less than 1% of the phenotypic variation, for which the GWAS sample size is under-powered.
“In contrast, other eye color loci reported [11] have been estimated each to explain less than 1% of the phenotypic variation, for which our GWAS sample size is under-powered.”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [11]
rs12913832 is a strong predictor of eye color; it alone explains 44-48% of the variance in quantitative measures of eye color in Dutch Europeans.
“rs12913832 is a strong predictor of eye color; it alone explains 44–48% of the variance in quantitative measures of eye color in Dutch Europeans [11].”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [11]
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- Authors
- Liu, F., Wollstein, A., Hysi, P. G., Ankra-Badu, G. A., Spector, T. D., Park, D., Zhu, G., Larsson, M., Duffy, D. L., Montgomery, G. W., Mackey, D. A., Walsh, S., Lao, O., Hofman, A., Rivadeneira, F., Vingerling, J. R., Uitterlinden, A. G., Martin, N. G., Hammond, C. J., & Kayser, M.
- Affiliations
- Erasmus MC (NL)
- University of Cologne (DE)
- King's College London (GB)
- QIMR Berghofer Medical Research Institute (AU)
- Lions Eye Institute (AU)
- Corresponding author
- Kayser, Manfred
- ORCID
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-05-06
- Volume
- 6
- Issue
- 5
- Pages
- e1000934
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2865509
- OpenAlex
- W2045107415
- Semantic Scholar
- 87d9d57d10ad482fb9aa1836da62b1416f0293f0
- Cited by
- 191
- References
- 49
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 13 · 2019: 16 · 2018: 12 · 2017: 10 · 2016: 11 · 2015: 12 · 2014: 14 · 2013: 20 · 2012: 17
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Helsingin Yliopisto
- Wellcome Trust (01254, 201865, 201413, HEALTH-F4-2007-201413)
- National Institute for Health and Care Research
- European Commission (QLG2-CT-2002-01254, 2007–2013, FP7 2007-2013, 201413, 201865, 01254, 014-93-015)
- ZonMw (050-060-810)
- Erasmus Universiteit Rotterdam
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810, FP7 2007-2013, 014-93-015, 911-03-012, 175.010.2005.011)
- Oogfonds
- Algemene Nederlandse Vereniging ter voorkoming van Blindheid
- Heidelberg Engineering
- Stichting Nederlands Oogheelkundig Onderzoek
- National Institutes of Health (389875, QLG2-CT-2002-01254)
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (G20234)
- Menzies Centre for Australian Studies, King's College London, University of London
- Australian Research Council (DP0343921)
- National Health and Medical Research Council (A7960034, 496739, 443036, A79906588, 389927, 389891, 552485, DP0212016, 552498, 442981, 389938, 241944, 339462, 442915, 389875, A79801419, 389892)
- Erasmus Universitair Medisch Centrum Rotterdam
- National Eye Institute (R01EY018246)
- National Cancer Institute (R01CA088363)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- iris color, eye color, genome-wide association study, LYST, complex traits
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Eye Color, Humans, Male, Middle Aged, Photography, Cohort Studies, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, Young Adult
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