It should be noted that our association analysis has been conducted on two moderately sized cohorts. The primary results were obtained in the larger UNC cohort that consisted of a homogeneous sub-sample of Caucasian females. The second UF cohort is smaller and consists of both genders. Although the association tests were highly significant in the first cohort only, and it is important to replicate our results in larger cohorts, the direction of effects was the same for both cohorts with respect to pain sensitivity, and associations with morphine response phenotypes were in the expected direction, suggesting that the T allele codes for a low-efficiency receptor variant. Furthermore, the validity of our findings is supported by molecular biology experiments presented here, which demonstrate the existence of human exon 13 and a functional effect of the identified SNP rs563649.
