Additionally, by haplotype analyses, we only found positive association results in our EA case-control samples (Table S2), but not in our AA and EA family samples (Table S1) or AA case-control samples (Table S2). There may be two possible explanations. One is that the five markers were not in compete LD (see Figure 1), so haplotype analysis (using the five markers) results cannot completely reflect single-marker analysis results (and have reduced power compared to those analyses because of the multiple haplotypes that must be considered in the context of dilution of results from whatever SNP or SNPs are actually driving the result). Another is that, in AA family or AA case-control samples, the association between POMC variants and substance dependence might be only at the individual marker level. Thus, the interactive effect of the five markers on substance dependence in AA population was not detectable by haplotype analyses.
