Strength of SNPs individually and as pairs, and the frequency of SNPs appearing in pairs detected in RA by and DSS. Manhattan plots for univariate and bivariate SNP and the frequency of SNPs occurrence in pairs detected in RA by and DSS. The Manhattan plots (a, c) show location and p-values of univariately significant SNPs (blue) and bivariately significant SNP pairs (green). Additionally, we mark the subset of SNP pairs that are also significant according to GSS (red circle). Each SNP pair generates two points. The frequency plots (b, d) show the number of reported pairs that each SNP appears in. The Manhattan plot for (a) indicates almost all reported pairs appear in two distinct bands across the genome. The frequency plot (b) indicates these pairs all involve one of the two most significant SNPs from univariate analysis (highlighted) and therefore majority of them are unlikely to be epistatic. Manhattan plot (c) shows the DSS filter eliminates the banding pattern seen for and the frequency plot (d) shows that a greater number of unique SNPs are present in detected pairs. Note in Manhattan plot (c), the p-values for univariate association are from SS test as DSS only applies to pairs. There is also no pairwise Bonferroni line shown because DSS is a heuristic rather than a calibrated p-value.