Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain

Molecular phenotypes associated with antipsychotic drugs in the human caudate nucleus

“…Genes differentially expressed by antipsychotic use in caudate are most enriched for specificity to D1 dopaminoceptive neurons (OR=3.50, P = 1.74e-82), D2 dopaminoceptive neurons (OR = 3.39, P=1.59e-77), and oligodendrocytes (OR=3.24,P = 7.84e-71). In DLPFC, they are most enriched for specificity to macrophages (OR= 3.69, P=8.70e-30), microglia (OR=7.22, P=6.99e-84), and T-cells (OR =2.43, P=2.94e-12), and depleted for specificity to oligodendrocytes (OR = 0.35, P = 2.60e-6) 18 (see Methods, Table S6, Table S7). Altogether, these results indicate that the caudate nucleus is strongly affected by antipsychotic drugs at a molecular level, and that these drugs have different effects in different areas of the brain.…”

“…Cell type enrichment of differentially expressed genes Cell-type specific gene expression data was taken from Tran et al 18 for the DLPFC and nucleus accumbens (a region which is also in the striatum with the caudate nucleus). We selected the top 2000 most cell type-specific genes for each considered cell type, which makes analyses across cell types more comparable (as many cell types had far more than 2000 DEGs that were significant).…”

De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations

“…Cell-type specific enrichment analysis of ZMYND8 was performed using singlecell RNA sequencing adult data across 5 brain regions (hippocampus, dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, nucleus accumbens and amygdala) and the single-cell expression profiles of approximately 40,000 cells were assessed from the developing human neocortex. 30,31 The cell-type specific expression data were log normalized and plotted using the ShinyApp interface and the aggregated cell data through the Cortical Development Expression (CoDeX) viewer.…”

“…ZMYND8 showed mild expression variation across brain regions limited to the fetal brain (Supplemental Figure 2). Cell-type specific expression measurements showed that ZMYND8 is ubiquitously expressed in both neurons and glia in the fetal neocortex 31 and in several regions of the adult human brain 30 (dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, nucleus accumbens and amygdala; Supplemental Figure 3A and B). These data are consistent with a key role for ZMYND8 during brain development.…”

EPIC: Inferring relevant cell types for complex traits by integrating genome-wide association studies and single-cell RNA sequencing

“…The various versions of the methods adopt different ways to select genes, transform the outcome and predictor variables, and include different sets of additional covariates [ 3 , 10 , 16 , 17 ]. While MAGMA-based methods have been successfully used in several studies [ 18 – 20 ], Yurko et al [ 21 ] examined the statistical foundation of MAGMA, and they identified an issue: type I error rate is inflated because the method incorrectly uses the Brown’s approximation when combining the SNP-level p -values. MAGMA’s implementation replaces the SNP-SNP correlation coefficient with its square, which serves as a rough correction yet masks the true LD structure.…”