First, we used a single-cell RNA-seq dataset that identified 88 broad categories of cell types (565 subclusters) in 690K single cells from 9 mouse brain regions (frontal cortex, striatum, globus pallidus externus/nucleus basalis, thalamus, hippocampus, posterior cortex, entopeduncular nucleus/subthalamic nucleus, substantia nigra/ventral tegmental area, and cerebellum) 41. We found similar patterns of association in this external dataset (Figure 3A, S14 and Table S7). Notably, for schizophrenia, we strongly replicated associations with neurons from the cortex, hippocampus and striatum. We also observed similar cell type associations for other psychiatric and cognitive traits (Figure 3A, S13, S14 and S15). For neurological disorders, we found that stroke was significantly associated with mural cells while Alzheimer’s disease was significantly associated with microglia (Figure S14). The associations of Parkinson’s disease with neurons from the substantia nigra and oligodendrocytes were significant at a nominal level in this dataset (P=0.006 for neurons from the substantia nigra, P=0.027 for oligodendrocytes using LDSC) (Table S3). By computing gene expression specificity within neurons, we replicated our previous findings that neurons from the cortex can be prioritized for multiple traits (schizophrenia, bipolar, educational attainment, intelligence, BMI, neuroticism, MDD, anorexia) (Figure S16).
