We used summary data-based Mendelian randomization (SMR)45,46 to identify putative causal relationships between SNPs and BD via gene expression by integrating the BD GWAS results with brain eQTL summary statistics from the PsychENCODE43 Consortium and blood eQTL summary statistics from the eQTLGen Consortium (31,684 whole blood samples)47. The eQTLGen results represent the largest existing eQTL study and provide independent eQTL data. Of the 32 genes fine-mapped with PIP > 0.7, 15 were significantly associated with BD in the SMR analyses and passed the HEIDI (heterogeneity in dependent instruments) test45,46, suggesting that their effect on BD is mediated via gene expression in the brain and/or blood (Supplementary Table 11). The genes located in genome-wide significant loci are labeled in Figure 1. Other significant genes included HTR6, DCLK3, HAPLN4 and PACSIN2.
