We asked whether the 19 genes identified by PWAS were enriched in a particular brain cell-type. Using human single-cell RNA sequencing data profiled from the dPFC32, we found that 10 of these 19 genes showed enrichment in specific cell types at FDR q <0.05 (adjusted for all 17,775 genes; Figure 2a; Supplementary Table 16a). Five genes were highly expressed in inhibitory neurons (CACNA2D2, CHD13, CNNM2, NEK4, SLC25A12) and three had enriched expression in excitatory neurons, albeit to a lesser degree than inhibitory neurons (CHD13, CNNM2, SLC25A12). To determine the specificity of this finding, we compared the enrichment of genes identified for BMI, WHR, and neuroticism for enrichment in inhibitory neurons. We found that depression genes were significantly enriched for inhibitory neurons compared to those for BMI (odds ratio (OR) = 5.6, p-value = 0.013) and WHR (OR = 9.5, p-value 0.004) but not to those for neuroticism (OR = 2.1, p-value = 0.450). Additionally, three genes were highly expressed in astrocytes (CTNND1, TKT, and TRPT1), one gene in oligodendrocytes (P2RX7), and one gene in microglia (LMBRD1; Figure 3a).
