Fig. 4

Fine-mapping causal variants for known and novel T2D genetic associations. a Distribution of sQTL causal posterior probabilities (CPP) across different genic and non-genic regions. P-values on top correspond to Mann-Whitney comparisons with non-genic regions. b eQTL causal posterior probabilities across epigenomic annotations. P-values on top correspond to comparisons with credible set variants that fall outside islet epigenomic annotations (closed chomatin regions). c, d For all T2D-associated loci that colocalize with an islet QTL, we examined all fine-mapped variants (99% credible sets in GWAS, GWAS_cred) and compared the distribution of T2D causal posterior probabilities for variants that are also fine-mapped QTL variants (QTL_cred) vs. those that were not fine-mapped QTL variants. Mann-Whitney p-values are provided. Boxplots show IQR without outliers although p-values were calculated using all data points. e, f Integration of T2D GWAS credible set variants with credible sets from colocalizing sQTLs and eQTLs increases fine mapping resolution. Bar plots show the number of independent signals that fall into different bins of number of candidate causal variants before and after restricting for QTL variants. G Fine-mapping an sQTL and T2D association in ERO1B. The splicing QTL effect on ERO1B is significant at FDR ≤ 1%; see Additional file 3: Table S2. The LocusZoom shows T2D association -log₁₀ p-values; credible set variants for GWAS and sQTLs are shown as circles, and other GWAS credible set variants as triangles. The color of dots reflects r² with the lead GWAS variant (in purple) and includes the best fine-mapped candidate causal sQTL (rs2477599). The bottom inset depicts the alternative splicing event, along with the candidate causal sQTL variant and clipDB RBP binding sites. Boxplots are as described in Figs. 1, 2, and 3.