Association test for the case of epistatic interaction. The population comprised 5,000 cases and 5,000 controls. Two DPLs with no marginal risk (RR=1), an epistatic interaction ( + 20% penetrance for the (3,3) combined genotype) and an additive G×E model (odds ratio (OR)=1.2) were used. The two DPLs are in two distinct genomic regions (Chr 8: 117,948,182 - 119,256,695 in yellow; Chr 10: 114,408,939 - 115,256,799 in cyan). In the upper panel, the Manhattan plot shows the significance of the association (−log10(p-value)) of each marker when tested individually (each dot represents a different marker). The red dashed line represents the significance threshold (0.05 after Bonferroni correction) and the green dashed lines mark the position of DPLs. In the middle panel, the r2 of each marker with the DPL in the same region is shown. In the bottom panel, the significance of the association for each 2-loci interaction (grey scale, nonsignificant; red scale, significant at a 0.05 level after Bonferroni correction) is shown.