Summary data-based Mendelian randomization (SMR) (v1.03)45,46 was applied to further investigate putative causal relationships between SNPs and BD via gene expression. SMR was performed using eQTL summary statistics from the eQTLGen (31,684 blood samples)47 and PsychENCODE43 consortia. SMR analysis is limited to transcripts with at least one significant cis-eQTL (P < 5 × 10−8) in each dataset (15,610 in eQTLGen; 10,871 in PsychENCODE). The Bonferroni-corrected significance threshold was P < 3.20 × 10−6 and P < 4.60 × 10−6 for eQTLGen and PsychENCODE, respectively. The significance threshold for the HEIDI test (heterogeneity in dependent instruments) was PHEIDI ≥ 0.0146. While the results of TWAS and SMR indicate an association between BD and gene expression, a non-significant HEIDI test additionally indicates either a direct causal role or a pleiotropic effect of the BD-associated SNPs on gene expression.
