We conducted tissue and cell-type enrichment analysis using published expression datasets including bulk RNA sequencing data from human tissues16 and single-cell RNA sequencing data from the adult mouse central and peripheral nervous system.17 Across human tissues, we found clearer enrichment patterns of MD SNP-heritability in neural tissues using the current GWAS association findings than those obtained from the previous two PGC Major Depressive Disorder (MDD) group analyses (Figure 3; Tables S5C–S5E). In the adult mouse central and peripheral nervous system, we found significant enrichment of MD SNP-heritability in 10 out of 39 cell types with two different methods (MAGMA and partitioned LD score regression [LDSC]; see key resources table). We confirmed all the cell types identified in the previous GWAS,7 including both excitatory and inhibitory neurons, but implicate multiple additional inhibitory neuron categories and peptidergic neurons.
