In terms of general biological insights, the most profound relate to inferences about the allelic architecture of common traits. The novel variants we have uncovered are characterized by modest effect size (that is, per-allele ORs between 1.2 and 1.5) and even these estimates are likely to be inflated114. We identified no additional common variants of very large effect (akin to HLA in T1D: Supplementary Fig. 15). The observed distribution of effect sizes is consistent with models based on theoretical considerations and empirical data from animal models87,115,116 that suggest that, for any given trait, there will be few (if any) large effects, a handful of modest effects and a substantial number of genes generating small or very small increases in disease risk.
