All 178 risk loci were fine-mapped (Figure 3 bottom; bottom panel); 1620 SNPs in the causal set out of 14,016 GWS hits have high posterior probability for causal relation with MDD-META (Figure 3 bottom; middle panel). The SNPs with casual posterior probability ≥ 30% were annotated with Combined Annotation Dependent Depletion (CADD) score.16 There were 19 SNPs with CADD scores >10, representing the top 1% of pathogenic variants across the human genome (Figure 3 bottom; top panel). These SNPs were annotated to genes positioned within ±100kb. We found 17 genes overlapping with significant genes identified from cross-tissue TWAS analysis. Each gene-tissue pair was tested for colocalization of the region for eQTL and GWAS. The coloc17 method tests probability of four hypotheses (H0–4). Of these, H4 tests the hypothesis that the same locus is shared between GWAS and tissue-specific eQTL. Loci that were found to have 80% or higher probability for H4 were compared, to understand the LD structure and most prominent variant being shared by GWAS and eQTL. These gene-tissue pairs were CCDC71-Amygdala (H4-PP: 93.1%), FADS1-Cerebellar hemisphere (H4-PP: 96.6%), SPPL3-Frontal Cortex (H4-PP: 83.9%), TRAF3-Hypothalamus (H4-PP: 95.2%) and LAMB2-whole blood (H4-PP: 79.9%) (Supplementary file 2).
