The neuronal chromatin landscape in brains from individuals with schizophrenia is linked to early fetal development. This study maps chromatin accessibility in neurons and glia in schizophrenia, revealing fetal-like regulatory patterns in adult neurons enriched for genetic risk variants, linking early brain development to schizophrenia pathogenesis.
We analyzed 1,393 chromatin accessibility profiles from two cortical regions of 469 individuals with and without serious mental illness to characterize sex-specific regulatory mechanisms. Our findings revealed distinct enhancer–promoter interactions, cis- and trans-regulatory domains, and X-chromosome inactivation–related pathways that collectively illuminate sex-dependent epigenomic architecture and its relevance to schizophrenia.
Here the authors provide a comprehensive transcriptomic dataset of human primary microglia for Alzheimer’s disease and healthy aging. They identify dysregulation of immune-related microglial functions as a hallmark of disease.
Cell-type-specific profiling of the human orbitofrontal cortex in major depressive disorder reveals unexpected glial dysregulation, identifying the astrocytic regulator ZBTB7A as a key driver of stress-related behavioral and molecular changes, thereby implicating astrocytes in MDD-linked OFC dysfunction.
We present a rigorously curated, population-scale multi-omics dataset of over 6.3 million single-nucleus transcriptomes from 1,494 human prefrontal cortex samples—including diverse neurodegenerative and psychiatric diagnoses with rich phenotypic data and comorbidities—publicly available to advance research into shared mechanisms across major brain disorders.
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.