In our study, T1D and CD, the conditions showing strongest familial aggregation (as quantified by their sibling relative risks, λs), generated the largest number of highly significant associations. This relationship was not sustained in comparisons between the other five diseases. It is important to recognize that the association signals so far identified account for only a small proportion of overall familiality. There is a disparity in scale between the modest locus-specific λs effects attributable to the identified associations (for instance, the prominent TCF7L2 signal for T2D translates into a λs of only 1.03) and the estimates of overall familiality that reflects the combined effects of all genes and shared family environment. These estimates demonstrate the limited potential of the variants thus far identified (singly or in combination) to provide clinically useful prediction of disease117,118
