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.

The genetic architecture of the network underlying flowering time variation inArabidopsis thaliana

“…This is very unlike most human traits, which mostly seem to vary due to pleiotropic mutations across the genome (BOYLE et al 2017), but more similar variation in adaptively varying traits like skin and eye color (BELEZA et al 2013). This agrees with the simple evolutionary expectation that adaptive variation should be less pleiotropic, whereas variation that is due to mutation-selection Regulation of flowering network 5 .…”

“…Using a variance component approach (SASAKI et al 2015), we estimated that alleles of the major flowering regulator FLC jointly explain 30% of the flowering time variation at 10 • C, with the rest of the genome accounting for 56%. The existence of a major allelic variation is similar to what has been seen for some other locally adaptive traits, e.g., skin and eye color in humans (BELEZA et al 2013), and is readily explained by selection maintaining variation. The high SNP heritability is presumably due to a combination of low environmental noise and high linkage disequilibrium leading to efficient capture of background genetic effects.…”

Assessing the photoprotective effects of red ochre on human skin by in vitro laboratory experiments

“…In addition to the incidence of lighter skin types amongst autochthonous groups along the southern and eastern coastline of South Africa and Mozambique 54 , the preservation of the SLC24A5, TYRP1 and KITLG alleles amongst sub-Saharan populations 20 suggests that these are ancestral southern African mutations. The skin colour of southern African MSA H. sapiens is therefore likely to have resembled the olive-brown 'Capoid' skin type IV (Von Luschan 16 to 21) typical of some indigenous southern African groups.…”

“…17,20 Unlike SLC45A2, which occurs only amongst Europeans, the SLC24A5, TYRP1 and KITLG mutations are present in a number of sub-Saharan populations. Although these alleles in all probability arose within and spread from Africa during early modern human migrations, some may result from a series of admixture events with groups containing Eurasian genetic ancestry.…”

A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set

“…25,26 The G allele is more frequent in African populations and the A allele is more frequent in European populations. Here, we used this SNP as a proxy for a trait in which the association with ancestry is strong and well established (skin color).…”