Extended Data Fig. 6: eTWAS associations between β-cell function (BCF) indices and UBE2E2 and ITFG3 islet gene expression.
Forest plots of the lead eTWAS associations for UBE2E2 (a) and ITFG3 (f). For each of the eight BCF traits and T2D, the square represents the β-estimate, and the error bars indicate the 95% confidence intervals. Square size is based on precision, and the effect allele and variant rsid are provided at the top. Summary statistics data were generated here or obtained from Mahajan, A. et al.55. Regional signal plots depict single-variant BCF GWAS meta-analyses P-values (-log10 scale, y-axis) and hg19 locations (x-axis) at the (b) UBE2E2 and (e) ITFG3 loci. LocusCompare scatter plots compare P-values from single-variant BCF GWAS meta-analyses and (c) UBE2E2 and (g) ITFG3 pancreatic islet eQTLs42 on the -log10 scale, respectively. The eTWAS P-value and the colocalization posterior probability (CPP) are provided at the top. Variants in regional signal plots and LocusCompare plots are coloured based on their LD correlation (r2) with the lead eTWAS association. Boxplots in panels (d) and (h) represent COMBAT normalized islet gene expression for each genotype of the lead eTWAS association for UBE2E2 and ITFG3, respectively. The data are derived from 399 human islet samples42. Boxplots show first (lower) quartile, median, and third (upper) quartile, and whiskers indicate 1.5 x interquartile range. Chromatin state profiles in panel (e) highlight the enhancer harbouring the ITFG3-eTWAS rs56038902 signal, which is proximal to the ITFG3 promoter.
