ArticleNature genetics2025
Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Microglial states revisited: from homeostasis to disease.Nature reviews. Neuroscience · 2026Review
- Shared genetic architecture across social disconnection, social disadvantage, and psychiatric and neurodevelopmental traits.European archives of psychiatry and clinical neuroscience · 2026Article
- Multiomic single-nucleus profiling reveals cell-type-specific epigenetic and transcriptional dysregulation in major depressive disorder brain.The international journal of neuropsychopharmacology · 2026Article
- Characterization of the chromosome 7 locus associated with suicidal behavior.Molecular psychiatry · 2026Article
- Neuronal Cell-Specific sc-eQTL and Integrative eQTL-pQTL Mendelian Randomization Prioritize CKAP2 as a Candidate Gene for Major Depressive Disorder.Journal of molecular neuroscience : MN · 2026Observational
- Microbiota-Driven microglia reprogramming reverses depressive-like behaviors through Peripheral-to-Central immune crosstalk.Molecular psychiatry · 2026Article
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Multi-omics characterization of astrocyte subtypes reveals spatially coordinated astrocyte downregulation in depression.bioRxiv : the preprint server for biology · 2026Article
- TranDep: a transcriptomics atlas of depression.Molecular psychiatry · 2026Article
- Cross-Platform and cross-species lipidomic profiling identifies promising biomarkers for adolescent major depressive disorder.Molecular psychiatry · 2026Article
- Mosaic: Single-Cell Atlas of Stress.Cells · 2026Review
- Pervasive neurovascular dysfunction in the ventromedial prefrontal cortex of female depressed suicides with a history of childhood abuse.Molecular psychiatry · 2026Article
- Differential Methylation by Early Life Adversity in the Future of Families Child Wellbeing Study.bioRxiv : the preprint server for biology · 2026Article
- Cellular heterogeneity and multicellular mechanisms in the pathogenesis of late-life depression: insights from single-cell and spatial multi-omics.Frontiers in immunology · 2026Review
- Defining functional states and roles of microglia in neuropsychiatric disorders.Frontiers in cellular neuroscience · 2026Review
- Similarities of neocortical deep layeriScience · 2025Article
- Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Genetic variants associated with major depressive disorder (MDD) are enriched in the regulatory genome. Here, we investigate gene-regulatory mechanisms underlying MDD compared to neurotypical controls by combining single-cell chromatin accessibility with gene expression in over 200,000 cells from the dorsolateral prefrontal cortex of 84 individuals. MDD-associated alterations in chromatin accessibility were prominent in deep-layer excitatory neurons characterized by transcription factor (TF) motif accessibility and binding of NR4A2, an activity-dependent TF reactive to stress. The same neurons were enriched for MDD-associated genetic variants, disrupting TF binding sites linked to genes that likely affect synaptic communication. Furthermore, a gray matter microglia cluster exhibited decreased accessibility in individuals with MDD at binding sites bound by TFs known to regulate immune homeostasis. Finally, we identified gene-regulatory effects of MDD-risk variants using sequence-based accessibility predictions, donor-specific genotypes and cell-based assays. These findings shed light on the cell types and regulatory mechanisms through which genetic variation may increase the risk of MDD.
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