title: Importance of nonsynonymous OCA2 variants in human eye color prediction.
abstract: BACKGROUND
  The color of the eyes is one of the most prominent phenotypes in humans and it is often used to describe the appearance of an individual. The intensity of pigmentation in the iris is strongly associated with one single-nucleotide polymorphism (SNP), rs12913832:A>G that is located in the promotor region of OCA2 (OMIM #611409). Nevertheless, many eye colors cannot be explained by only considering rs12913832:A>G.
  
  
  METHODS
  In this study, we searched for additional variants in OCA2 to explain human eye color by sequencing a 500 kbp region, encompassing OCA2 and its promotor region.
  
  
  RESULTS
  We identified three nonsynonymous OCA2 variants as important for eye color, including rs1800407:G>A (p.Arg419Gln) and two variants, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile), not previously described as important for eye color variation. It was shown that estimated haplotypes consisting of four variants (rs12913832:A>G, rs1800407:G>A (p.Arg419Gln), rs74653330:A>T (p.Ala481Thr), and rs121918166:G>A (p.Val443Ile)) explained 75.6% (adjusted R (2) = 0.76) of normal eye color variation, whereas rs12913832:A>G alone explained 68.8% (adjusted R (2) = 0.69). Moreover, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) had a measurable effect on quantitative skin color (P = 0.008).
  
  
  CONCLUSIONS
  Our data showed that rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) have a measurable effect on normal pigmentation variation.
authors.affiliation: Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
authors.forename: Jeppe D
authors.initials: JD
authors.lastname: Andersen
authors.affiliation: Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Pietroni
authors.affiliation: Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Johansen
authors.affiliation: Department of Mathematical Sciences Aalborg University DK-9000 Aalborg Denmark.
authors.forename: Mikkel M
authors.initials: MM
authors.lastname: Andersen
authors.affiliation: Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
authors.forename: Vania
authors.initials: V
authors.lastname: Pereira
authors.affiliation: Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Børsting
authors.affiliation: Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Morling
keywords: Eye color; OCA2; forensic DNA phenotyping; nonsynonymous variants; pigmentation; rs74653330 and rs121918166; skin color