ArticleGenome medicine2020
A chromosomal connectome for psychiatric and metabolic risk variants in adult dopaminergic neurons.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Clinical Characterization of Copy Number Variants Associated With Neurodevelopmental Disorders in a Large-scale Multiancestry Biobank.JAMA psychiatry · 2022Pooled it
- The distinct effects of metabolic syndrome on negative symptoms and on antipsychotic therapy of schizophrenia involve insular volume, functional connectivity, and genetic polymorphisms.Translational psychiatry · 2026Article
- Downregulated transcription in chromosomal domains of midbrain dopamine neurons linked to schizophrenia.Nature communications · 2026Article
- 3D genetic architecture of schizophrenia risk across three neuronal subtypes.Molecular psychiatry · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Functional implications of polygenic risk for schizophrenia in human neurons.Nature communications · 2026Article
- SATB2 organizes the 3D genome architecture of cognition in cortical neurons.Molecular cell · 2024Article
- Sex differences in the association between metabolic disorder and inflammatory cytokines in Han Chinese patients with chronic schizophrenia.Frontiers in psychiatry · 2024Article
- Invited Expert Opinion- Bioinformatic and Limitation Directives to Help Adopt Genetic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Required Analytic Evidence to Induce Dopamine Homeostatsis.Medical research archives · 2023Article
- Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.Nature communications · 2023Article
- Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk.Molecular psychiatry · 2023Article
- Review
- High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci.Nature communications · 2022Article
- Chromatin architecture in addiction circuitry identifies risk genes and potential biological mechanisms underlying cigarette smoking and alcohol use traits.Molecular psychiatry · 2022Article
- Cis-regulatory hubs: a new 3D model of complex disease genetics with an application to schizophrenia.Life science alliance · 2022Article
- Understanding Regulatory Mechanisms of Brain Function and Disease through 3D Genome Organization.Genes · 2022Review
- Reward Deficiency Syndrome (RDS) Surprisingly Is Evolutionary and Found Everywhere: Is It "Blowin' in the Wind"?Journal of personalized medicine · 2022Article
- Advances in profiling chromatin architecture shed light on the regulatory dynamics underlying brain disorders.Seminars in cell & developmental biology · 2022Review
- Chromatin Profiling Techniques: Exploring the Chromatin Environment and Its Contributions to Complex Traits.International journal of molecular sciences · 2021Review
- Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders.Nature communications · 2021Article
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Authors and funding
28 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundMidbrain dopaminergic neurons (MDN) represent 0.0005% of the brain's neuronal population and mediate cognition, food intake, and metabolism. MDN are also posited to underlay the neurobiological dysfunction of schizophrenia (SCZ), a severe neuropsychiatric disorder that is characterized by psychosis as well as multifactorial medical co-morbidities, including metabolic disease, contributing to markedly increased morbidity and mortality. Paradoxically, however, the genetic risk sequences of psychosis and traits associated with metabolic disease, such as body mass, show very limited overlap.
methodsWe investigated the genomic interaction of SCZ with medical conditions and traits, including body mass index (BMI), by exploring the MDN's "spatial genome," including chromosomal contact landscapes as a critical layer of cell type-specific epigenomic regulation. Low-input Hi-C protocols were applied to 5-10 × 10
resultsThe Hi-C-reconstructed MDN spatial genome revealed 11 "Euclidean hot spots" of clustered chromatin domains harboring risk sequences for SCZ and elevated BMI. Inter- and intra-chromosomal contacts interconnecting SCZ and BMI risk sequences showed massive enrichment for brain-specific expression quantitative trait loci (eQTL), with gene ontologies, regulatory motifs and proteomic interactions related to adipogenesis and lipid regulation, dopaminergic neurogenesis and neuronal connectivity, and reward- and addiction-related pathways.
conclusionsWe uncovered shared nuclear topographies of cognitive and metabolic risk variants. More broadly, our PsychENCODE sponsored Hi-C study offers a novel genomic approach for the study of psychiatric and medical co-morbidities constrained by limited overlap of their respective genetic risk architectures on the linear genome.
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