The relationships between OPRM1 genetic variants and pain scores were first examined using overall tests for haplotypic associations with the composite haplotype method (CHM) (52) in sliding windows of one to 12 SNPs (Table 3). The CHM is designed for determining associations due to multiple interacting SNPs and is applicable regardless of the linkage disequilibrium (LD) between the tested SNPs. CHM is a flexible extension of our earlier approach, termed the haplotype trend regression (HTR) (53). The difference between the two approaches lies in that the HTR considers joint frequencies of alleles that reside on the same haplotype, whereas the CHM considers the sum of joint frequencies that reside on the same as well as on two different haplotypes within individuals. Thus, the CHM is readily applicable to sets of SNPs that span separate haplotype blocks. Moreover, while the CHM can be used to detect haplotypic effects, it is also able to capture epistatic effects due to interactions between two haplotypes in a diplotype. We conducted two types of haplotype association analysis. ‘Overall’ CHM tests in sliding windows of varying
