Simultaneous profiling of RNA and chromatin accessibility in single nuclei isolated from human postnatal brain regions from infancy to late adulthood identifies key cellular regulators and nominates target genes and mechanisms for brain-related diseases and disorders.
A multi-ancestry study of bipolar disorder (n = 158,036 cases, 2.8M controls) identified 298 loci, 36 genes, ancestry-specific associations, and subtype-specific genetic architecture, revealing convergent variant signals and cell-type involvement in its pathophysiology.
This review explores how chromatin accessibility profiling, particularly ATAC-seq, combined with single-cell technologies, GWAS, and transcriptomics, has advanced our understanding of the noncoding genome's role in neuropsychiatric and neurodegenerative diseases
Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder, characterized by motor and cognitive impairments, that affects 1% of the population over the age of 60. The pathogenesis of PD is complex and remains largely unknown. Due to the …
Brain gene regulation is key for neuropsychiatric disorders. Here, the authors show that profiling gene expression and chromatin states in 25 brain regions enables enhancer-promoter mapping at isoform resolution, improving genetic fine-mapping.
ARC-SV, a novel probabilistic method for detecting complex structural variations (cxSVs), revealed cxSVs as a major driver of human genetic diversity and implicated them in neuropsychiatric disorders through effects on neural genes, chromatin accessibility, and gene expression in brain regions and cell types.
Multi-omic profiling of matched brain and peripheral tissues offer rare opportunities to uncover extra-CNS drivers of Alzheimer’s pathobiology. Here, authors report an Alzheimer’s linked CD83(+) microglia subtype that is associated with immunoglobulin IgG4 production in the transverse colon.
We present a comprehensive catalog that captures variation in the human brain regulome, which illuminates the cell type–specific molecular mechanisms that underlie neuropsychiatric and neurodegenerative disorders. Our work highlights an approach to move from statistical associations from large-scale GWASs to functionally validated variants and molecular mechanisms of disease.
Our population-scale single-cell resource for the human brain can help facilitate precision-medicine approaches for neuropsychiatric disorders, especially by prioritizing follow-up genes and drug targets linked to cell types.
Our results provide a valuable resource to investigate the molecular pathophysiology of schizophrenia at single-cell resolution, offering insights into preferential dysregulation of specific neuronal populations and their potential role in mediating genetic risk. Together, they suggest convergence of etiological genetic risk factors, neuronal transcriptional dysregulation, and symptomatic manifestation in schizophrenia.