Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

Sandra Beleza; Nicholas A. Johnson; Sophie I. Candille; Devin M. Absher; Marc A. Coram; Jailson Lopes; Joana Campos; Isabel Inês Araújo; Tovi M. Anderson; Bjarni J. Vilhjálmsson; Magnus Nordborg; António Correia e Silva; Mark D. Shriver; Jorge Rocha; Gregory S. Barsh; Hua Tang

doi:10.1371/journal.pgen.1003372

Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

Sandra Beleza, Nicholas A. Johnson, Sophie I. Candille, Devin M. Absher, Marc A. Coram, Jailson Lopes, Joana Campos, Isabel Inês Araújo, Tovi M. Anderson, Bjarni J. Vilhjálmsson, Magnus Nordborg, António Correia e Silva, Mark D. Shriver, Jorge Rocha, Gregory S. Barsh, Hua Tang

Anthropology

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10^-62, SLC24A5 P = 9.6×10^-9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10^-27, TYR P = 1.1×10^-9, APBA2[OCA2] P = 1.5×10^-8, SLC45A2 P = 6×10^-9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

Original language	English (US)
Article number	e1003372
Journal	PLoS genetics
Volume	9
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1003372
State	Published - 2013

All Science Journal Classification (ASJC) codes

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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Beleza, S., Johnson, N. A., Candille, S. I., Absher, D. M., Coram, M. A., Lopes, J., Campos, J., Araújo, I. I., Anderson, T. M., Vilhjálmsson, B. J., Nordborg, M., Correia e Silva, A., Shriver, M. D., Rocha, J., Barsh, G. S., & Tang, H. (2013). Genetic Architecture of Skin and Eye Color in an African-European Admixed Population. PLoS genetics, 9(3), Article e1003372. https://doi.org/10.1371/journal.pgen.1003372

@article{80e957758b304c3398123311444796e1,

title = "Genetic Architecture of Skin and Eye Color in an African-European Admixed Population",

abstract = "Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10-62, SLC24A5 P = 9.6×10-9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10-27, TYR P = 1.1×10-9, APBA2[OCA2] P = 1.5×10-8, SLC45A2 P = 6×10-9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.",

author = "Sandra Beleza and Johnson, {Nicholas A.} and Candille, {Sophie I.} and Absher, {Devin M.} and Coram, {Marc A.} and Jailson Lopes and Joana Campos and Ara{\'u}jo, {Isabel In{\^e}s} and Anderson, {Tovi M.} and Vilhj{\'a}lmsson, {Bjarni J.} and Magnus Nordborg and {Correia e Silva}, Ant{\'o}nio and Shriver, {Mark D.} and Jorge Rocha and Barsh, {Gregory S.} and Hua Tang",

year = "2013",

doi = "10.1371/journal.pgen.1003372",

language = "English (US)",

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Beleza, S, Johnson, NA, Candille, SI, Absher, DM, Coram, MA, Lopes, J, Campos, J, Araújo, II, Anderson, TM, Vilhjálmsson, BJ, Nordborg, M, Correia e Silva, A, Shriver, MD, Rocha, J, Barsh, GS & Tang, H 2013, 'Genetic Architecture of Skin and Eye Color in an African-European Admixed Population', PLoS genetics, vol. 9, no. 3, e1003372. https://doi.org/10.1371/journal.pgen.1003372

TY - JOUR

T1 - Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

AU - Beleza, Sandra

AU - Johnson, Nicholas A.

AU - Candille, Sophie I.

AU - Absher, Devin M.

AU - Coram, Marc A.

AU - Lopes, Jailson

AU - Campos, Joana

AU - Araújo, Isabel Inês

AU - Anderson, Tovi M.

AU - Vilhjálmsson, Bjarni J.

AU - Nordborg, Magnus

AU - Correia e Silva, António

AU - Shriver, Mark D.

AU - Rocha, Jorge

AU - Barsh, Gregory S.

AU - Tang, Hua

PY - 2013

Y1 - 2013

N2 - Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10-62, SLC24A5 P = 9.6×10-9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10-27, TYR P = 1.1×10-9, APBA2[OCA2] P = 1.5×10-8, SLC45A2 P = 6×10-9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

AB - Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10-62, SLC24A5 P = 9.6×10-9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10-27, TYR P = 1.1×10-9, APBA2[OCA2] P = 1.5×10-8, SLC45A2 P = 6×10-9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

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U2 - 10.1371/journal.pgen.1003372

DO - 10.1371/journal.pgen.1003372

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JO - PLoS genetics

JF - PLoS genetics

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Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

Abstract

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