All the 19 proteins identified in the discovery depression PWAS were profiled at the mRNA-level but only 14 had significant SNP-based heritability estimates for mRNAs (Supplementary Table 13). The TWAS using FUSION found that 13 of these 14 genes had their cis-regulated mRNA levels associated with depression at nominal significance level, and 11 of these 13 had consistent directions of effect for the mRNA and protein (Table 1; Supplementary Table 13a). All 11 genes passed SMR test but only 10 passed HEIDI test. CNNM2 did not pass the HEIDI test (HEIDI p=0.033). For the 11 genes with evidence for association with depression at both the mRNA and protein levels, SMR for two molecular traits31 (i.e., mRNA and protein) suggests that 9 of these 11 genes regulate brain protein abundance via their regulation of brain mRNA expression level (Supplementary Table 15).
