GWAS enrichment analysis

We tested for enrichment of fine-mapped T2D risk variants from the DIAMANTE consortium for beta cell cCREs defining the beta-1 and beta-2 subtype as well as cCREs with differential activity in T2D. For each set of cCREs, we calculated the cumulative posterior probability of association (cPPA) of all fine-mapped variants overlapping cCREs. We then generated a null distribution of cPPA by randomly selecting the same number of cCREs from the set of all beta cell cCREs across 100,000 permutations. We calculated a p-value as the number of permutations with a higher cPPA than for the observed set of cCREs. We further computed an odds ratio as cPPA_obs*(cPPA_max-cPPA_mean)/cPPA_mean*(cPPA_max-cPPA_obs), where cPPA_obs was the observed cPPA, cPPA_max is the maximum possible cPPA for that number of sites and cPPA_mean is the average cPPA from the null distribution, and took the natural log of the odds ratio.