Skin Pigmentation study with SNP Genotypes (Array), CNV Genotypes data on dbGaP (225 participants)

phs001753 — Rapid Evolution of a Skin Lightening Allele in Southern African KhoeSan

<p>The genetic architecture and polygenicity of skin pigmentation is explored in KhoeSan communities, including Nama individuals whose phenotype and genotype data are provided in this dataset. By pairing genotypes and quantitative spectrophotometric skin pigmentation phenotypes, we show that skin pigmentation is highly heritable in KhoeSan, yet known pigmentation loci only explains a small fraction of the phenotypic variance. Using genome-wide association analyses, we identified both canonical and non-canonical skin pigmentation loci. We show that this phenotype is more polygenic and complex than previously characterized. (Martin et al., Cell 2017. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/29195075">29195075</a>)</p> <p>Following up on the top associated signal with large effect size in the gene SLC24A5, we demonstrate that the canonical Eurasian nonsynonymous allele was introduced into KhoeSan via a recent migration ~2 kya and was under extremely strong selection. The derived allele was present at high frequency despite controlling for gene flow. With high-throughput sequences in the captured SLC24A5 region, we show that the most common derived haplotype is identical amongst Europeans, eastern African and KhoeSan. Using 4-population demographic simulations with selection, we show that the allele was introduced into the KhoeSan only 2,000 ya via a back-to-Africa migration and then experienced a selective sweep.</p>