Extended Data Fig. 7: PPA calculation workflow.
From: Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
a, We estimated the PPAs for nonsynonymous variants in our sequence analysis based on concordance with independent exome array data and previously published6,78,80 estimates of the fraction of causal coding associations (Methods). b, PPA estimates for nonsynonymous variants within T2D GWAS loci are shown as a function of P value (right y axis, black line; 95% confidence interval, grey shading) together with the total number of such variants (left y axis, red line). c, For variants outside of T2D GWAS loci, we developed a method to further compute Bayes factors, which measure the odds of true and causal association, as a function of P value, using a model of the prior odds of true and causal association for variants in GWAS loci (Methods). d, These Bayes factors can be combined with a subjective prior belief in the T2D relevance of a gene (y axis) to produce the estimated posterior probability of true and causal association for any nonsynonymous variant in the exome-sequence dataset based on its observed log10(P) (x axis). Posterior estimates are shaded proportional to value (red, low; white, high). Values are shown for the default modelling assumptions of 33% of missense variants that caused gene inactivation and 30% of true missense associations that represented the causal variant.
