Extended Data Fig. 7: sTWAS associations between β-cell function (BCF) traits and islet mRNA splicing of G6PC2 and GRB10 genes.
Forest plots of the lead sTWAS associations at G6PC2 (a) and GRB10 (e). For each of the eight BCF traits and glycaemic traits, the square shows the β-estimate, and the error bars indicate the 95% confidence intervals. Summary statistics data were generated in this study or obtained from large-scale transancestral meta-analyses (European-based estimates from Chen, J. et al.49). Square sizes are based on precision. LocusCompare scatter plots compare the -log10 P-values for sQTLs of (b-c) G6PC2 and (g) GRB10 from Atla, A. et al.42, on the y-axis, with the -log10 P-values from BCF single-variant GWAS meta-analyses, on the x-axis. Variants are coloured based on the LD correlation (r2) with the lead sTWAS association. The sTWAS P-value and the colocalization posterior probability (CPP) are provided at the top. In panels (d) and (h), boxplots show normalized, batch-corrected junction PSI values stratified by the genotype of the lead sTWAS association. The data are derived from 399 human islet samples42. Boxplots show the first (lower) quartile, median, and third (upper) quartile, with whiskers extending to 1.5 times the interquartile range. IGV was used for the visualization of splice junctions depicted at the top of the boxplots, with arrow indicating the splice junction selected from sTWAS analysis. Regional signal plot at panel (f) shows single-variant BCF-GWAS meta-analyses P-values (-log10 scale, y-axis) and hg19 locations (x-axis) for the GRB10 locus.
