Co-localization of expression quantitative trait loci (eQTL) signatures from platelets in GeneSTAR European Americans

A subset of 180 TOPMed GeneSTAR European Americans samples also had RNA-seq data generated using platelets. eQTL analysis was performed as previously described⁵⁴. Here, formal Bayesian co-localization was performed using the coloc^55–57 package in R for each of the 16 independent loci (Table 1) against all gene transcripts where there was at least one SNP with an eQTL p value p < 0.003125 (0.05/16) for the specific gene within 20 KB of the peak variant. This yielded 10 locus-gene pairs (Supplementary Table ⁴). coloc tests five mutually exclusive hypotheses: H0, no GWAS and no eQTL association; H1, association with GWAS, but no eQTL; H2, association with eQTL, but no GWAS; H3, eQTL and GWAS association, but with two independent causal variants; and H4, shared causal variants for both eQTL and GWAS. The main interest is to assess whether there is a shared causal variant between eQTL and GWAS (i.e., H4). The package provides five posterior probabilities for these hypotheses (PP0, PP1, PP2, PP3, and PP4) and PP4 of >75% is considered evidence of a colocalization of GWAS and eQTL. Posterior probabilities for individual variants were evaluated once PP4 was met.