A separate question relates to the best models for the way in which different loci combine to affect susceptibility to a disease, and as a consequence on the extent to which methods explicitly allowing interactions between loci should be employed to detect associations110. None of the analyses reported here includes such interactions, so we are not well placed to address the general question. Nonetheless, within each collection with multiple associated regions (CD, T1D and T2D) we considered all pairs of non-MHC SNPs in Table 3 and looked for a departure from the model in which the two loci combine to increase log-odds in an additive fashion. We found suggestive evidence of a departure from multilocus additivity between rs1000113 and rs10761659 in CD (unadjusted P value = 0.002) and between rs9465871 and rs4506565 in T2D (unadjusted P value = 0.004). Further investigation of this question, preferably on unbiased sets of disease loci found through the application of single locus and interaction-based approaches, would seem warranted.
