Prediction of Human Pigmentation Traits from DNA Polymorphisms


Driven by recent evolutionary history, pigmentation traits significantly contribute to the most obvious parts of the overall human phenotypic diversity with skin colour varying between worldwide individuals, while eye and hair colour differences only exist in individuals of European (and neighbouring region) descent. Genetic association studies have discovered various DNA variants that together explain large proportion of phenotypic variance in eye, hair and skin colouration. Besides providing leads in the molecular understanding of human pigmentation, multiple associated DNA variants have also been used for prediction modelling of pigmentation traits. The success of DNA‐based pigmentation prediction laid the foundation for a new subfield of forensic genetics known as Forensic DNA Phenotyping, which aims to help finding unknown perpetrators. Pigmentation DNA prediction is further relevant in anthropological research from old and ancient human remains for reconstructing colour phenotypes of deceased persons including those of historical importance.

Key Concepts

  • Driven by recent evolutionary history, differences in pigmentation significantly contribute to the phenotypic diversity in humans.
  • Eye, hair and skin colour reflect complex traits with multiple genes and environmental factors determining phenotypic variation distributed differently around the world.
  • Gene mapping studies identified a number of pigmentation genes that typically but not necessarily determine all three pigmentation traits in humans.
  • Multiple pigmentation‐associated DNA variants have proven useful to predict all three human pigmentation traits with varying accuracies.
  • Several DNA test systems are available for accurate prediction of blue and brown eyes, while for other eye colours further research is needed.
  • Available DNA test systems for hair colour provide accurate prediction of red and (albeit less so) of black hair, while the DNA prediction of blond and brown hair is troubled by age‐dependent hair colour changes in some (but not all) individuals not yet understood on the molecular level.
  • Of the three human pigmentation traits, DNA prediction of skin colour is least advanced, requiring considerable further research.
  • Current DNA prediction on the level of categorical eye, hair and skin colour shall be improved towards more detailed colour phenotypes, if the necessary DNA predictors become available via dedicated future research.
  • Forensic science is a major recipient of pigmentation predictive DNA tests, where they are used to trace unknown perpetrators unidentifiable via conventional DNA profiling.
  • Pigmentation DNA prediction is also relevant in anthropological and human evolutionary research particularly from old and ancient human remains.

Keywords: human appearance; eye colour; hair colour; skin colour; pigmentation genetics; genotype to phenotype; prediction modelling; molecular anthropology; forensic genetics; forensic DNA phenotyping

Figure 1. Illustration of HIrisPlex‐based eye and hair colour DNA prediction. Eye and hair images of 12 individuals selected to vary strongly in hair and eye colour with their eye colour probabilities as obtained with the enhanced IrisPlex model and their hair colour probabilities obtained with the enhanced HIrisPlex model ( from complete 24‐loci DNA profiles generated with the HIrisPlex genotyping assay. Those probabilities that led to the predicted eye and hair colour categories are highlighted in grey following guidelines described in Walsh et al. (, ). Individual numbering is 1–6 on the left side and 7–12 on the right side. DNA‐based prediction conclusions are as follows: 1: black hair and brown eyes, 2: dark brown/black hair and brown eyes, 3: dark brown/black hair and blue eyes, 4: brown/dark brown hair and blue eyes, 5: Brown/medium brown hair and brown eyes, 6: Brown hair and brown eyes (likely with non‐brown parts), 7: Blond/dark blond hair and blue eyes, 8: blond hair and blue eyes, 9: blond/dark blond hair and blue eyes, 10: red hair and blue eyes, 11: red hair and brown eyes (likely with non‐brown parts), 12: red hair and blue eyes. Reproduced from Kayser () © Elsevier.


Allentoft ME, Sikora M, Sjögren K‐G, et al. (2015) Population genomics of Bronze Age in Eurasia. Nature 522: 167–172.

Allwood JS and Harbison S (2013) SNP model development for the prediction of eye colour in New Zealand. Forensic Science International: Genetics 7: 444–52.

Bogdanowicz W, Allen M, Branicki W, et al. (2009) Genetic identification of putative remains of the famous astronomer Nicolaus Copernicus. Proceedings of the National Academy of Sciences of the United States of America 106: 12279–82.

Branicki W, Brudnik U, Kupiec T, Wolańska‐Nowak P and Wojas‐Pelc A (2007) Determination of phenotype associated SNPs in the MC1R gene. Journal of Forensic Science 52: 349–54.

Branicki W, Brudnik U and Wojas‐Pelc A (2009) Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Annals of Human Genetics 73: 160–70.

Branicki W, Liu F, van Duijn K, et al. (2011) Model‐based prediction of human hair colour using DNA variants. Human Genetics 129: 443–54.

Chaitanya L, Walsh S, Andersen JD, et al. (2014) Collaborative EDNAP exercise on the IrisPlex system for DNA‐based prediction of human eye colour. Forensic Science International: Genetics 11: 241–251.

Cerqueira CCS, Paixão‐Côrtes VR, Zambra FMB, et al. (2012) Predicting homo pigmentation phenotype through genomic data: From Neanderthal to James Watson. American Journal of Human Biology 24: 705–709.

Draus‐Barini J, Walsh S, Pośpiech E, et al. (2013) Bona fide colour: DNA prediction of human eye and hair colour from ancient and contemporary skeletal remains. Investigative Genetics 4: 3.

Duffy DL, Montgomery GW, Chen W, et al. (2007) A three‐single‐nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye‐colour variation. American Journal of Human Genetics 80: 241–52.

Eiberg H and Mohr J (1996) Assignment of genes coding for brown eye colour (BEY2) and brown hair colour (HCL3) on chromosome 15q. European Journal of Human Genetics 4: 237–41.

Eiberg H, Troelsen J, Nielsen M, et al. (2008) Blue eye colour in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Human Genetics 123: 177–87.

Frudakis T, Thomas M, Gaskin Z, et al. (2003) Sequences associated with human iris pigmentation. Genetics 165: 2071–83.

Graf J, Hodgson R and van Daal A (2005) Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Human Mutation 25: 278–84.

Grimes EA, Noake PJ, Dixon L and Urquhart A (2001) Sequence polymorphism in the human melanocortin 1 receptor gene as an indicator of the red hair phenotype. Forensic Science International 122: 124–9.

Han J, Kraft P, Nan H, et al. (2008) A genome‐wide association study identifies novel alleles associated with hair colour and skin pigmentation. PLoS Genetics 4: e1000074.

Hart KL, Kimura SL, Mushailov V, et al. (2013) Improved eye‐ and skin‐colour prediction based on 8 SNPs. Croatian Medical Journal 54: 248–256.

Jacobs LC, Wollstein A, Lao O, et al. (2013) Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin colour variation in Europeans. Human Genetics 132: 147–158.

Kanetsky PA, Swoyer J, Panossian S, et al. (2002) A polymorphism in the agouti signaling protein gene is assoviated with human pigmentation. American Journal of Human Genetics 70: 770–775.

Kayser M and de Knijff P (2011a) Improving human forensics through advances in genetics, genomics and molecular biology. Nature Reviews Genetics 12: 179–92.

Kayser M, Liu F, Janssens AC, et al. (2008) Three genome‐wide association studies and a linkage analysis identify HERC2 as a human iris colour gene. American Journal of Human Genetics 82: 411–23.

Kayser M (2015a) Forensic DNA phenotyping: predicting human appearance from crime scene material for investigative purposes. Forensic Science International Genetics. 10.1016/j.fsigen.2015.02.003.

Keller A, Graefen A, Ball M, et al. (2012) New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole‐genome sequencing. Nature Communications 3: 698.

Kenny EE, Timpson NJ, Sikora M, et al. (2012) Melanesian blond hair is caused by an amino acid change in TYRP1. Science 336: 554.

King TE, Fortes GG, Balaresque P, et al. (2014) Identification of the remains of King Richard III. Nature Communications 5: 5631.

Lamason RL, Mohideen MA, Mest JR, et al. (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310: 1782–6.

Lalueza‐Fox C, Römpler H, Caramelli D, et al. (2007) A melanocortin 1 receptor allele suggests varying pigmentation among Neanderthals. Science 318: 1453–5.

Liu F, van Duijn K, Vingerling JR, et al. (2009) Eye colour and the prediction of complex phenotypes from genotypes. Current Biology 19: R192–3.

Liu F, Wollstein A, Hysi PG, et al. (2010) Digital quantification of human eye colour highlights genetic association of three new loci. PLoS Genetics 6: e1000934.

Liu F, Visser M, Duffy DL, et al. (2015) Genetics of skin colour variation in Europeans: genome‐wide association studies with functional follow‐up. Human Genetics. DOI: 10.1007/s00439-015-1559-0.

Maroñas O, Phillips C, Söchtig J, et al. (2014) Development of a forensic skin colour predictive test. Forensic Science International: Genetics 13: 34–44.

Mártinez‐García M and Montoliu L (2013) Albinism in Europe. Journal of Dermatology 40: 319–24.

Mengel‐From J, Børsting C, Sanchez JJ, Eiberg H and Morling N (2010) Human eye colour and HERC2, OCA2 and MATP. Forensic Science International: Genetics 4: 323–8.

Pośpiech E, Draus‐Barini J, Kupiec T, et al. (2012) Prediction of eye color from genetic data using Bayesian approach. Journal of Forensic Sciences 57: 880–886.

Rasmussen M, Li Y, Lindgreen S, et al. (2010) Ancient human genome sequence of an extinct Palaeo‐Eskimo. Nature 463: 757–62.

Rebbeck TR, Kanetsky PA, Walker AH, et al. (2002) P gene as an inherited biomarker of human eye colour. Cancer Epidemiology, Biomarkers & Prevention 11: 782–4.

Ruiz Y, Phillips C, Gomez‐Tato A, et al. (2013) Further development of forensic eye colour predictive tests. Forensic Science International: Genetics 7: 28–40.

Spichenok O, Budimlija ZM, Mitchell AA, et al. (2011) Prediction of eye and skin colour in diverse populations using seven SNPs. Forensic Science International: Genetics 5: 472–8.

Stokowski RP, Pant PV, Dadd T, et al. (2007) A genomewide association study of skin pigmentation in a South Asian population. The American Journal of Human Genetics 81: 1119–32.

Sturm RA, Duffy DL, Zhao ZZ, et al. (2008) A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue‐brown eye colour. The American Journal of Human Genetics 82: 424–31.

Sulem P, Gudbjartsson DF, Stacey SN, et al. (2007) Genetic determinants of hair, eye and skin pigmentation in Europeans. Nature Genetics 39: 1443–52.

Valenzuela RK, Henderson MS, Walsh MH, et al. (2010) Predicting phenotype from genotype: normal pigmentation. Journal of Forensic Sciences 55: 315–22.

Valverde P, Healy E, Jackson I, Rees JL and Thody AJ (1995) Variants of the melanocyte‐stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nature Genetics 11: 328–30.

Visser M, Kayser M and Palstra RJ (2012) HERC2 rs12913832 modulates human pigmentation by attenuating chromatin‐loop formation between a long‐range enhancer and the OCA2 promoter. Genome Research 22: 446–55.

Walsh S, Liu F, Ballantyne KN, et al. (2011a) IrisPlex: a sensitive DNA tool for accurate prediction of blue and brown eye colour in the absence of ancestry information. Forensic Science International: Genetics 5: 170–80.

Walsh S, Lindenbergh A, Zuniga SB, et al. (2011b) Developmental validation of the IrisPlex system: determination of blue and brown eye colour for forensic intelligence. Forensic Science International: Genetics 5: 464–471.

Walsh S, Wollstein A, Liu F, et al. (2012) DNA‐based eye colour prediction across Europe with the IrisPlex system. Forensic Science International: Genetics 6: 330–40.

Walsh S, Liu F, Wollstein A, et al. (2013) The HIrisPlex system for simultaneous prediction of hair and eye colour from DNA. Forensic Science International: Genetics 7: 98–115.

Walsh S, Chaitanya L, Clarisse L, et al. (2014) Developmental validation of the HIrisPlex system: DNA‐based eye and hair colour prediction for forensic and anthropological usage. Forensic Science International: Genetics 9: 150–61.

Wilde S, Timpson A, Kirsanow K, et al. (2014) Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y. Proceedings of the National Academy of Sciences of the United States of America 111 (13): 4832–4837.

Further Reading

Jablonski NG (2012) Living Colour: The Biological and Social Meaning of Skin Colour. Berkeley: University of California Press.

Kayser M (2015b) Forensic DNA phenotyping: predicting human appearance from crime scene material for investigative purposes. Forensic Science International: Genetics. 10.1016/j.fsigen.2015.02.003.

Kayser M and de Knijff P (2011b) Improving human forensics through advances in genetics, genomics and molecular biology. Nature Reviews Genetics 12: 179–92.

Liu F, Wen B and Kayser M (2013) Colourful DNA polymorphisms in humans. Seminars in Cell & Developmental Biology 24: 562–575.

Sturm RA (2009) Molecular genetics of human pigmentation diversity. Human Molecular Genetics 18: R9–17.

Sturm RA and Duffy DL (2012) Human pigmentation genes under environmental selection. Genome Biology 13: 948.

Visser M, Kayser M, Grosveld F and Palstra R‐J (2014) Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation. Pigment Cell & Melanoma Research 27: 169–177.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Branicki, Wojciech, and Kayser, Manfred(Oct 2015) Prediction of Human Pigmentation Traits from DNA Polymorphisms. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023851]