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.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America. sbeleza@stanford.edu
authors.forename: Sandra
authors.initials: S
authors.lastname: Beleza
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Sophie I
authors.initials: SI
authors.lastname: Candille
authors.forename: Devin M
authors.initials: DM
authors.lastname: Absher
authors.forename: Marc A
authors.initials: MA
authors.lastname: Coram
authors.forename: Jailson
authors.initials: J
authors.lastname: Lopes
authors.forename: Joana
authors.initials: J
authors.lastname: Campos
authors.forename: Isabel Inês
authors.initials: II
authors.lastname: Araújo
authors.forename: Tovi M
authors.initials: TM
authors.lastname: Anderson
authors.forename: Bjarni J
authors.initials: BJ
authors.lastname: Vilhjálmsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordborg
authors.forename: António
authors.initials: A
authors.lastname: Correia E Silva
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Jorge
authors.initials: J
authors.lastname: Rocha
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D055726:Cabo Verde; D005127:Eye Color / Q000235:genetics*; D005838:Genotype; D006200:Hair Color / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012880:Skin Pigmentation / Q000235:genetics*; D044465:White People / Q000235:genetics*
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