A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia

Nat Commun. 2019 Jan 21;10(1):358. doi: 10.1038/s41467-018-08147-0.


We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People
  • Biological Evolution
  • Epistasis, Genetic*
  • Ethnicity
  • Eye Color / genetics*
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetics, Population
  • Genome, Human*
  • Genome-Wide Association Study
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Latin America
  • Male
  • Membrane Proteins / genetics
  • Membrane Transport Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Receptor, Metabotropic Glutamate 5 / genetics
  • Skin Pigmentation / genetics*
  • Ubiquitin-Protein Ligases
  • White People


  • GRM5 protein, human
  • Guanine Nucleotide Exchange Factors
  • MFSD12 protein, human
  • Membrane Proteins
  • Membrane Transport Proteins
  • OCA2 protein, human
  • Receptor, Metabotropic Glutamate 5
  • HERC2 protein, human
  • Ubiquitin-Protein Ligases