Original Investigation

Human Genetics

, Volume 131, Issue 5, pp 683-696

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

A global view of the OCA2-HERC2 region and pigmentation

  • Michael P. DonnellyAffiliated withDepartment of Genetics, School of Medicine, Yale University
  • , Peristera PaschouAffiliated withDepartment of Molecular Biology and Genetics, Democritus University of Thrace
  • , Elena GrigorenkoAffiliated withChild Study Center, School of Medicine, Yale University
  • , David GurwitzAffiliated withNational Laboratory for the Genetics of Israeli Populations, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University
  • , Csaba BartaAffiliated withInstitute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University
  • , Ru-Band LuAffiliated withDepartment of Psychiatry, College of Medicine and Hospital, National Cheng-Kung University
  • , Olga V. ZhukovaAffiliated withN.I. Vavilov Institute of General Genetics RAS
  • , Jong-Jin KimAffiliated withDNA Analysis Division, National Institute of Scientific Investigation
  • , Marcello SiniscalcoAffiliated withLaboratory of Statistical Genetics, The Rockefeller University
    • , Maria NewAffiliated withGenetics and Genomic Sciences, The Mount Sinai School of Medicine
    • , Hui LiAffiliated withMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University
    • , Sylvester L. B. KajunaAffiliated withDepartment of Biochemistry and Molecular Biology, Hubert Kairuki Memorial University
    • , Vangelis G. ManolopoulosAffiliated withLaboratory of Pharmacology, Medical School, Democritus University of Thrace
    • , William C. SpeedAffiliated withDepartment of Genetics, School of Medicine, Yale University
    • , Andrew J. PakstisAffiliated withDepartment of Genetics, School of Medicine, Yale University
    • , Judith R. KiddAffiliated withDepartment of Genetics, School of Medicine, Yale University
    • , Kenneth K. KiddAffiliated withDepartment of Genetics, School of Medicine, Yale University Email author 


Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160–170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535–542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele.