SynthesisJAMA psychiatry2018
DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies.
Synthesis in JAMA psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 7 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Childhood internalising symptoms at ages 3 and 6: a meta-analysis of epigenome-wide associations from cord and peripheral blood.Journal of child psychology and psychiatry, and allied disciplines · 2026Pooled it
- Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts.Genome medicine · 2024Pooled it
- Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study.Epigenetics · 2022Pooled it
- DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.Molecular psychiatry · 2021Pooled it
- Physical Activity and Genome-wide DNA Methylation: The REgistre GIroní del COR Study.Medicine and science in sports and exercise · 2020Pooled it
- Longitudinal epigenome-wide association studies of three male military cohorts reveal multiple CpG sites associated with post-traumatic stress disorder.Clinical epigenetics · 2020Pooled it
- Systems Approach to Identify Common Genes and Pathways Associated with Response to Selective Serotonin Reuptake Inhibitors and Major Depression Risk.International journal of molecular sciences · 2019Pooled it
- Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial.Translational psychiatry · 2022Trial
- Liquid biopsy: current applications and future directions.Molecular biomedicine · 2026Review
- Associations of stable psychological traits with multi-omic subtypes of Alzheimer's dementia.Translational psychiatry · 2026Article
- Shared genetic architecture and pathways linking major depressive disorder and autoimmune thyroid disease: insights from common and rare variants.Translational psychiatry · 2026Article
- Clinical and biological markers of electroconvulsive therapy effectiveness: a narrative review.Translational psychiatry · 2026Review
- Article
- Biological, Psychosocial, and Microbial Determinants of Childhood-Onset Obsessive-Compulsive Disorder: A Narrative Review.Children (Basel, Switzerland) · 2025Review
- Article
- Whole exome sequencing identified six novel genes for depressive symptoms.Molecular psychiatry · 2025Article
- Genome-wide methylome-based molecular pathologies associated with depression and suicide.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Genetic Alterations in War-Related Post-Traumatic Stress Disorder: A Systematic Review.Bulletin of emergency and trauma · 2025Review
- A methylome-wide association study of major depression with out-of-sample case-control classification and trans-ancestry comparison.Nature. Mental health · 2025Article
- Epigenomic and clinical analyses of striatal DAT binding in healthy individuals reveal well-known loci of Parkinson's disease.Heliyon · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
49 authors at 19 institutions in 6 countries.
Funding
Abstract
Importance: Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers. Objective: To identify epigenetic mechanisms underlying depression in middle-aged and elderly persons, using DNA methylation in blood. Design, Setting, and Participants: To date, the first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was conducted. The discovery EWAS included 7948 individuals of European origin from 9 population-based cohorts. Participants who were assessed for both depressive symptoms and whole-blood DNA methylation were included in the study. Results of EWAS were pooled using sample-size weighted meta-analysis. Replication of the top epigenetic sites was performed in 3308 individuals of African American and European origin from 2 population-based cohorts. Main Outcomes and Measures: Whole-blood DNA methylation levels were assayed with Illumina-Infinium Human Methylation 450K BeadChip and depressive symptoms were assessed by questionnaire. Results: The discovery cohorts consisted of 7948 individuals (4104 [51.6%] women) with a mean (SD) age of 65.4 (5.8) years. The replication cohort consisted of 3308 individuals (2456 [74.2%] women) with a mean (SD) age of 60.3 (6.4) years. The EWAS identified methylation of 3 CpG sites to be significantly associated with increased depressive symptoms: cg04987734 (P = 1.57 × 10-08; n = 11 256; CDC42BPB gene), cg12325605 (P = 5.24 × 10-09; n = 11 256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P = 5.99 × 10-08; n = 11 256; chromosome = 15q26.1). The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 × 10-03) and of ARHGEF3 in fibroblasts (effect, -0.48; P = 9.8 × 10-04) was associated with major depression. Conclusions and Relevance: This study identifies 3 methylated sites associated with depressive symptoms. All 3 findings point toward axon guidance as the common disrupted pathway in depression. The findings provide new insights into the molecular mechanisms underlying the complex pathophysiology of depression. Further research is warranted to determine the utility of these findings as biomarkers of depression and evaluate any potential role in the pathophysiology of depression and their downstream clinical effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.