Supplementary Figure 5: Distribution of LD between the top associated GWAS SNPs and the simulated causal eQTLs.

The results are from an SMR analysis of real GWAS data for five complex traits (Supplementary Table 6) and simulated eQTL data. The eQTL data were simulated on the basis of real genotypes, mimicking the Westra study but with the causal variants of cis-eQTLs randomly placed across the genome (see the Supplementary Note for details). There were a number of simulated probes that passed the SMR and HEIDI tests (Supplementary Table 14). For these probes, the overlaps between the GWAS and eQTL signals are due to the strong LD between the GWAS causal variants and the causal eQTLs. Unfortunately, the GWAS causal variants are unknown. Shown are LD r² values for the top associated GWAS SNPs and the simulated causal eQTLs in these probe regions, which are likely to be underestimations of LD between the causal variants. For regions where there were multiple independent GWAS signals as indicated by a GCTA-COJO analysis⁶, we selected the top GWAS SNP, conditioning the secondary GWAS signal (a secondary GWAS signal was defined as the top associated GWAS SNP in the region when conditioning on the GWAS SNP used in the SMR test).