ArticleBiological psychiatry2020
Cell Type-Specific Methylome-wide Association Studies Implicate Neurotrophin and Innate Immune Signaling in Major Depressive Disorder.
Article in Biological psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Epigenome-wide DNA methylation in externalizing behaviours: A review and combined analysis.Neuroscience and biobehavioral reviews · 2023Pooled it
- Epigenetic dysregulation in depression: molecular mechanisms, clinical biomarkers, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Article
- A large-scale DNA methylation study of alcohol use identified robust associations and cell-type specific insights.Molecular psychiatry · 2026Article
- Identification and Validation of Antidepressant Small Molecules Using Bioinformatics and Mouse Depression Models.Drug design, development and therapy · 2025Article
- A neurotrophin functioning with a Toll regulates structural plasticity in a dopaminergic circuit.eLife · 2024Article
- m6A/m1A/m5C-Associated Methylation Alterations and Immune Profile in MDD.Molecular neurobiology · 2024Article
- The researcher's guide to selecting biomarkers in mental health studies.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Investigating neonatal health risk variables through cell-type specific methylome-wide association studies.Clinical epigenetics · 2024Article
- Does biological age mediate the relationship between childhood adversity and depression? Insights from the Detroit Neighborhood Health Study.Social science & medicine (1982) · 2024Article
- Methylome-wide association studies of psychiatric disorders.EC psychology and psychiatry · 2024Article
- Methylome-wide association study of anxiety disorders.Molecular psychiatry · 2023Article
- Genes implicated by a methylome-wide schizophrenia study in neonatal blood show differential expression in adult brain samples.Molecular psychiatry · 2023Article
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
- Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims.International journal of molecular sciences · 2022Article
- Review
- Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance.Molecular psychiatry · 2022Article
- Epigenome-wide DNA methylation in obsessive-compulsive disorder.Translational psychiatry · 2022Article
- Challenges in Analyzing Functional Epigenetic Data in Perspective of Adolescent Psychiatric Health.International journal of molecular sciences · 2022Review
- Dual methylation and hydroxymethylation study of alcohol use disorder.Addiction biology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundWe sought to characterize methylation changes in brain and blood associated with major depressive disorder (MDD). As analyses of bulk tissue may obscure association signals and hamper the biological interpretation of findings, these changes were studied on a cell type-specific level.
methodsIn 3 collections of human postmortem brain (n = 206) and 1 collection of blood samples (N = 1132) of MDD cases and controls, we used epigenomic deconvolution to perform cell type-specific methylome-wide association studies within subpopulations of neurons/glia for the brain data and granulocytes/T cells/B cells/monocytes for the blood data. Sorted neurons/glia from a fourth postmortem brain collection (n = 58) were used for validation purposes.
resultsCell type-specific methylome-wide association studies identified multiple findings in neurons/glia that were detected across brain collections and were reproducible in physically sorted nuclei. Cell type-specific analyses in blood samples identified methylome-wide significant associations in T cells, monocytes, and whole blood that replicated findings from a past methylation study of MDD. Pathway analyses implicated p75 neurotrophin receptor/nerve growth factor signaling and innate immune toll-like receptor signaling in MDD. Top results in neurons, glia, bulk brain, T cells, monocytes, and whole blood were enriched for genes supported by genome-wide association studies for MDD and other psychiatric disorders.
conclusionsWe both replicated and identified novel MDD-methylation associations in human brain and blood samples at a cell type-specific level. Our results provide mechanistic insights into how the immune system may interact with the brain to affect MDD susceptibility. Importantly, our findings involved associations with MDD in human samples that implicated many closely related biological pathways. These disease-linked sites and pathways represent promising new therapeutic targets for MDD.
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