title: Multilocus OCA2 genotypes specify human iris colors.
abstract: Human iris color is a quantitative, multifactorial phenotype that exhibits quasi-Mendelian inheritance. Recent studies have shown that OCA2 polymorphism underlies most of the natural variability in human iris pigmentation but to date, only a few associated polymorphisms in this gene have been described. Herein, we describe an iris color score (C) for quantifying iris melanin content in-silico and undertake a more detailed survey of the OCA2 locus (n = 271 SNPs). In 1,317 subjects, we confirmed six previously described associations and identified another 27 strongly associated with C that were not explained by continental population stratification (OR 1.5-17.9, P = 0.03 to <0.001). Haplotype analysis with respect to these 33 SNPs revealed six haplotype blocks and 11 hap-tags within these blocks. To identify genetic features for best-predicting iris color, we selected sets of SNPs by parsing P values among possible combinations and identified four discontinuous and non-overlapping sets across the LD blocks (p-Selected SNP sets). In a second, partially overlapping sample of 1,072, samples with matching diplotypes comprised of these p-Selected OCA2 SNPs exhibited a rate of C concordance of 96.3% (n = 82), which was significantly greater than that obtained from randomly selected samples (62.6%, n = 246, P<0.0001). In contrast, the rate of C concordance using diplotypes comprised of the 11 identified hap-tags was only 83.7%, and that obtained using diplotypes comprised of all 33 SNPs organized as contiguous sets along the locus (defined by the LD block structure) was only 93.3%. These results confirm that OCA2 is the major human iris color gene and suggest that using an empirical database-driven system, genotypes from a modest number of SNPs within this gene can be used to accurately predict iris melanin content from DNA.
authors.affiliation: DNAPrint Genomics, Inc, 1621 W. University Pkwy, Sarasota, FL 34243, USA. tonynfrudakis@dnaprint.com
authors.forename: Tony
authors.initials: T
authors.lastname: Frudakis
authors.forename: Timothy
authors.initials: T
authors.lastname: Terravainen
authors.forename: Matthew
authors.initials: M
authors.lastname: Thomas
mesh_terms: D000483:Alleles; D030561:Databases, Nucleic Acid; D005127:Eye Color / Q000235:genetics* / Q000502:physiology; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008543:Melanins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics
chemical_list: D008543:Melanins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human