Fig. 3
Type 2 diabetes risk signals map in islet enhancers. a Genetic variants in islet active regulatory elements genome-wide were enriched for T2D risk, with strongest enrichment in active enhancer (EnhA1) elements. Values represent log enrichment and 95% CI, and are colored blue where the 95% CI does not overlap 0. b The effects of variants in active enhancer (EnhA1) and promoter (TssA) elements on T2D risk were stronger among those in chromatin loops, whereas other elements were enriched for T2D outside of loops. Values represent log enrichment and 95% CI, and are colored blue where the 95% CI does not overlap 0. c Over 30% of the total causal probability across 107 known T2D risk signals mapped in islet enhancer elements. d Clustering of known T2D signals based on islet and coding annotations identified 30 signals with likely causal variants in islet enhancers. e A significantly higher percentage of T2D islet enhancer signals were associated with IGTT-based insulin secretion phenotypes than un-annotated T2D signals (Chi-square **P < 0.001). f Number of variants in the 99% credible sets for the 30 T2D islet enhancer signals based on genetic fine-mapping alone (genetic), genetic fine-mapping, including functional priors (+priors). g T2D causal variant rs7732130 at the 5q13 locus near ZBED3/PDE8B mapped in an islet active enhancer. h rs7732130 has allelic effects on enhancer activity in the islet cell line MIN6 (N = 3), where the T2D risk allele and reference (ref) G has higher activity than the alternate (alt) allele A. Values represent mean and SD. T-test **P < 0.001, ***P < 0.0001. Boxplots show the median, and third and first quartiles. Source data are provided as a source data file
