Fig. 1: Summary of all RG loci identified in this study.
a, Circular Manhattan plot summarizing findings from this study. In the outermost layer, gene names of the 133 distinct RG signals are labeled with different colors indicating the following three clusters defined in cluster analysis: 1a/1b, metabolic syndrome; 2a/2b, insulin release versus insulin action (with additional effects on inflammatory bowel disease for cluster 2a) and 3, defects of insulin secretion. Asterisks annotate RG signals that are new for glycemic traits. Track 1 shows RG Manhattan plot reporting −log10(P value) for RG GWAS meta-analysis. Signals reaching genome-wide significance (P < 5.0 × 10−8) are colored in red. Crosses annotate loci that show evidence of sex heterogeneity (Psex-dimorphic < 5.0 × 10−8 and Psex-heterogeneity < 0.05); blue crosses for larger effects in men, green crosses for larger effects in women. Track 2 shows the effects of the 133 independent RG signals on four GIP/GLP-1-related traits GWAS. The colors of the dotted lines indicate four GIP/GLP-1-related traits: gray dot, signals reaching P < 0.010 for a GIP/GLP-1-related trait; red dot, lead SNP has a significant effect on GIP/GLP-1-related trait (Bonferroni corrected P < 1.0 × 10−4). Track 3 shows the effects (−log10(P value)) of the 133 independent RG signals on 113 glycan PheWAS. Track 4 shows the effects (−log10(P value)) of the 133 independent RG signals on 210 gut-microbiome PheWAS. Track 5 shows MetaXcan results for ten selected tissues for RG GWAS meta-analysis; signals colocalizing with genes (Bonferroni corrected P < 9.0 × 10−7) are plotted for each tissue. All P values were calculated from the two-sided z statistics computed by dividing the estimated coefficients by the estimated standard error, without adjustment. b, Credible set analysis of RG associations in the European ancestry meta-analysis. Variants from each of the RG signal credible sets are grouped based on their posterior probability (the percentiles labeled on the sides of the bar). SNP variants with posterior probability >80%, along with their locus names, are provided. All variants from the credible set of lead signals are highlighted in bold.
