Additionally, we searched for potential functional variants in COMT by identifying possible signatures of positive natural selection. The three derived alleles in the most common EA15-SNP haplotype, in addition to rs4680 (Val108/158Met), may be functional variants, and are candidate risk loci for behavioral phenotypes where the Val108/158Met polymorphism has been implicated but does not fully explain phenotypic variation. We studied the decay over distance of haplotype homozygosity from a core haplotype of these three SNPs within the larger 15-SNP haplotypes. Under neutral conditions it is expected that haplotype frequency is a function of haplotype age; older haplotypes will be higher in frequency than those that have arisen recently. It is also expected that recombination, over time, will result in decreased homozygosity with increasing distance from a core haplotype. Natural selection may explain the departure from neutrality seen in a high frequency core haplotype for which homozygosity has been maintained rather than broken down by recombination relative to other core haplotypes. The SNPs we identified in COMT for which the derived alleles make up a high-frequency haplotype with relatively greater homozygosity
