Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up

Hum Genet. 2015 Aug;134(8):823-35. doi: 10.1007/s00439-015-1559-0. Epub 2015 May 12.

Abstract

In the International Visible Trait Genetics (VisiGen) Consortium, we investigated the genetics of human skin color by combining a series of genome-wide association studies (GWAS) in a total of 17,262 Europeans with functional follow-up of discovered loci. Our GWAS provide the first genome-wide significant evidence for chromosome 20q11.22 harboring the ASIP gene being explicitly associated with skin color in Europeans. In addition, genomic loci at 5p13.2 (SLC45A2), 6p25.3 (IRF4), 15q13.1 (HERC2/OCA2), and 16q24.3 (MC1R) were confirmed to be involved in skin coloration in Europeans. In follow-up gene expression and regulation studies of 22 genes in 20q11.22, we highlighted two novel genes EIF2S2 and GSS, serving as competing functional candidates in this region and providing future research lines. A genetically inferred skin color score obtained from the 9 top-associated SNPs from 9 genes in 940 worldwide samples (HGDP-CEPH) showed a clear gradual pattern in Western Eurasians similar to the distribution of physical skin color, suggesting the used 9 SNPs as suitable markers for DNA prediction of skin color in Europeans and neighboring populations, relevant in future forensic and anthropological investigations.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti Signaling Protein / genetics
  • Antigens, Neoplasm / genetics
  • Chromosomes, Human / genetics*
  • European Continental Ancestry Group / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Loci*
  • Genome-Wide Association Study*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Interferon Regulatory Factors / genetics
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Skin Pigmentation / genetics*
  • Ubiquitin-Protein Ligases
  • United Kingdom

Substances

  • ASIP protein, human
  • Agouti Signaling Protein
  • Antigens, Neoplasm
  • Guanine Nucleotide Exchange Factors
  • Interferon Regulatory Factors
  • Membrane Transport Proteins
  • SLC45A2 protein, human
  • interferon regulatory factor-4
  • HERC2 protein, human
  • Ubiquitin-Protein Ligases