ArticleMolecular psychiatry2022
Genetic heterogeneity and subtypes of major depression.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 8 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- A systematic narrative review of the form, process, and function of sensory hyposensitivity in depression.Translational psychiatry · 2026Pooled it
- Identification of a diagnosis-selective neurobiological substrate for bipolar disorder, major depressive disorder, and schizophrenia: a meta-analysis of 57,717 subjects.Psychological medicine · 2026Pooled it
- Effect of Anti-Inflammatory Treatment on Depressive Symptom Severity and Anhedonia in Depressed Individuals With Elevated Inflammation: Systematic Review and Meta-Analysis of Randomized Controlled Trials.The American journal of psychiatry · 2026Pooled it
- Harnessing digital health interventions to address the heterogeneity of depression: a systematic review.Frontiers in digital health · 2025Pooled it
- A Meta-Analysis of Magnetic Resonance Spectroscopy Studies on Glutamatergic Neurometabolite Levels in Major Depressive Disorder.Depression and anxiety · 2025Pooled it
- The disappointment centre of the brain gets exciting: a systematic review of habenula dysfunction in depression.Translational psychiatry · 2024Pooled it
- Postpartum and non-postpartum depression: a population-based matched case-control study comparing polygenic risk scores for severe mental disorders.Translational psychiatry · 2023Pooled it
- Polygenicity of Comorbid Depression in Multiple Sclerosis.Neurology · 2023Pooled it
- Distinct depressive-like behavioural phenotypes in mice exhibit unique patterns of transcriptional perturbations across habenular cell subtypes.Molecular psychiatry · 2026Article
- Social disconnection integrates genetic and proteomic risks in suicidal ideation and depression.Translational psychiatry · 2026Article
- A genome-wide investigation of depression among individuals with and without irritability.Molecular psychiatry · 2026Article
- Gut microbiota-driven metabolites modulate the development of stress-related mental disorders.Translational psychiatry · 2026Review
- Atypical energy-related symptoms define biologically distinct subtypes of major depressive disorder.medRxiv : the preprint server for health sciences · 2026Article
- The many-to-many problem of endophenotypes in psychiatry - a biological perspective.Molecular psychiatry · 2026Review
- The Impact of Pre-Existing Psychiatric Disorders on Gastric Cancer Stage and Mortality in Older Adults.Cancer medicine · 2026Article
- An exploratory data-driven stratification of depression based on functional network connectivity and symptom profiles suggests heterogeneous responses to iTBS.BMC psychiatry · 2026Article
- Can Psychiatric Genetics Advance Without Incorporating a Life Course Perspective?Biological psychiatry · 2026Review
- Symptom-specific genetics reveal heterogeneity within major depressive disorder.medRxiv : the preprint server for health sciences · 2026Article
- Genetic Signal Augmentation of Childhood-Onset and Treatment-Resistant Major Depression Reveals Distinct Biological Disorders.medRxiv : the preprint server for health sciences · 2026Article
- Associations of polygenic risk scores for major depression and depression severity: an investigation of 105 623 individuals with 16 years follow-up.Molecular psychiatry · 2026Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
Major depression (MD) is a heterogeneous disorder; however, the extent to which genetic factors distinguish MD patient subgroups (genetic heterogeneity) remains uncertain. This study sought evidence for genetic heterogeneity in MD. Using UK Biobank cohort, the authors defined 16 MD subtypes within eight comparison groups (vegetative symptoms, symptom severity, comorbid anxiety disorder, age at onset, recurrence, suicidality, impairment, and postpartum depression; N ~ 3000-47000). To compare genetic component of these subtypes, subtype-specific genome-wide association studies were performed to estimate SNP-heritability, and genetic correlations within subtype comparison and with other related disorders/traits. The findings indicated that MD subtypes were divergent in their SNP-heritability, and genetic correlations both within subtype comparisons and with other related disorders/traits. Three subtype comparisons (vegetative symptoms, age at onset, and impairment) showed significant differences in SNP-heritability; while genetic correlations within subtype comparisons ranged from 0.55 to 0.86, suggesting genetic profiles are only partially shared among MD subtypes. Furthermore, subtypes that are more clinically challenging, e.g., early-onset, recurrent, suicidal, more severely impaired, had stronger genetic correlations with other psychiatric disorders. MD with atypical-like features showed a positive genetic correlation (+0.40) with BMI while a negative correlation (-0.09) was found in those without atypical-like features. Novel genomic loci with subtype-specific effects were identified. These results provide the most comprehensive evidence to date for genetic heterogeneity within MD, and suggest that the phenotypic complexity of MD can be effectively reduced by studying the subtypes which share partially distinct etiologies.
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