The associations observed in the present study seem unlikely to be spurious for a number of reasons. First, as noted above, the association signals were replicable between case-control and family based samples. Second, the association signals of SNP3 and SNP8 were observed across five phenotype groups that were defined based on comorbidity with CD, i.e., total CD, CDnoAD, CDnoOD, CDnoMD and CDnoR-SD (Figure 3). The consistency across these five groups not only argues against a false positive association but suggested that the association signals were from CD rather than from other types of SD. Third, another CD-related trait, CIP, also showed association with SNP8 in haplotypewise analysis (Pglobal=0.003), providing further evidence for an association between CNR1 and CD. Fourth, the association signals were consistent when we used different analytic approaches. Genotype frequency comparison analysis showed that the genotype frequency of SNP8^T/T in CD cases was significantly higher than in controls among subjects carrying SNP3^G; Logistic regression analysis showed that the interaction between SNP3^G+ and SNP8^T/T significantly increased the risk for CD; and haplotypewise analysis also consistently showed that the GT
