Polygenic dissection of major depression clinical heterogeneity.
paper
Cited
Public
- Authors
- Milaneschi, Y; Lamers, F; Peyrot, W J; Abdellaoui, A; Willemsen, G; Hottenga, J-J; Jansen, R; Mbarek, H; Dehghan, A; Lu, C; CHARGE inflammation working group; Boomsma, D I; Penninx, B W J H
- Year
- 2016
- Journal
- Molecular psychiatry
- PMID
- 26122587
- DOI
- 10.1038/mp.2015.86
- PMCID
- PMC5546325
The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the polygenic features of MDD and two common clinical subtypes (typical and atypical) defined by symptom profiles in a large sample of adults with established diagnoses. Data were from 1530 patients of the Netherlands Study of Depression and Anxiety (NESDA) and 1700 controls mainly from the Netherlands Twin Register (NTR). Diagnoses of MDD and its subtypes were based on DSM-IV symptoms. Genetic overlap of MDD and subtypes with psychiatric (MDD, bipolar disorder, schizophrenia) and metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated from meta-analysis results of large international consortia. Single nucleotide polymorphism (SNP)-heritability of MDD and subtypes was also estimated. MDD was associated with psychiatric GPRS, while no association was found for GPRS of metabolic traits. MDD subtypes had differential polygenic signatures: typical was strongly associated with schizophrenia GPRS (odds ratio (OR)=1.54, P=7.8e-9), while atypical was additionally associated with BMI (OR=1.29, P=2.7e-4) and triglycerides (OR=1.21, P=0.006) GPRS. Similar results were found when only the highly discriminatory symptoms of appetite/weight were used to define subtypes. SNP-heritability was 32% for MDD, 38% and 43% for subtypes with, respectively, decreased (typical) and increased (atypical) appetite/weight. In conclusion, MDD subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes. Disentangling MDD heterogeneity may help the psychiatric field moving forward in the search for molecular roots of depression.
Associations of GPRS for psychiatric and metabolic traits with MDD and subtypes (severe typical and severe atypical).Results (Odds Ratios and 95% Confidence Intervals) from binary (MDD: 1,530 cases) and multinomial (subtypes: 228 severe typical, 251 severe atypical) logistic regressions (reference: 1,700 controls) adjusted for year of birth, gender and three ancestry-informative principal components
Proportions of variance explained on the liability scale for MDD and subtypes (severe typical and severe atypical) by the GPRS for psychiatric and metabolic traits. Explained variance based on R2 coefficient proposed by Lee at al.(39); prevalences for linear transformation into liability scale: MDD K=0.18, severe typical K=0.035, severe atypical K=0.038
1β20 of 34
Next β
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Associations of polygenic risk scores for major depression and depression severity: an investigation of 105 623 individuals with 16 years follow-up. | Haram M et al. | β | 2026 | β |
| Atypical Depression Is Associated With a Distinct Clinical, Neurobiological, Treatment Response, and Polygenic Risk Profile. | Shin M et al. | β | 2026 | β |
| Inflammation, metabolic dysregulation, and depression profiles related to anhedonia and atypical, energy-related symptoms. | Zwiep JC et al. | β | 2026 | β |
| A combination of potential psychobiotics alleviates anxiety and depression behaviors induced by chronic unpredictable mild stress. | Meng C et al. | β | 2025 | β |
| Association between triglyceride-glucose (TyG) index and risk of depression in middle-aged and elderly Chinese adults: Evidence from a large national cohort study. | Xu ZY et al. | β | 2025 | β |
| Correlation analysis between clinical effective emotional treatment and plasma N-methyl-D-aspartate receptor function-related indexes. | Feng Z et al. | β | 2025 | β |
| Depression with immuno-metabolic dysregulation: Testing pragmatic criteria to stratify patients. | Zwiep JC et al. | β | 2025 | β |
| Familial and genetic relationships of major depressive disorders and adiposity markers in the community. | Berney A et al. | β | 2025 | β |
| Genetic factors and symptom dimensions associated with antidepressant treatment outcomes: clues for new potential therapeutic targets? | Martone A et al. | β | 2025 | β |
| Genetics and Neurobiology of Treatment-Resistant Depression-A Review. | PΕaza O et al. | β | 2025 | β |
| Morbidity-bridging metabolic pathways: linking early cardiovascular disease risk and depression symptoms using a multi-modal approach. | Koloi A et al. | β | 2025 | β |
| Polygenic Risk Score Analysis of Antidepressant Treatment Outcomes: A CAN-BIND-1 Study Report: Analyse des rΓ©sultats du traitement antidΓ©presseur Γ l'aide des scores de risque polygΓ©niques : Rapport sur l'Γ©tude CAN-BIND-1. | Magarbeh L et al. | β | 2025 | β |
| The differential orbitofrontal activity and connectivity between atypical and typical major depressive disorder. | Guo ZP et al. | β | 2025 | β |
| The rationale for subtyping depression into atypical and melancholic in research and clinical settings: A narrative review. | Preisig M et al. | β | 2025 | β |
| Treatment-resistant depression: role of genetic factors in the perspective of clinical stratification and treatment personalisation. | Fabbri C | β | 2025 | β |
| Adenylate cyclase 3: a potential genetic link between obesity and major depressive disorder. | Fitzpatrick M et al. | β | 2024 | β |
| The Association of Genetic Polymorphisms and Atypical Depression in Adults: A Systematic Review. | Galiautdinova A et al. | β | 2024 | β |
| A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity. | Baltramonaityte V et al. | β | 2023 | β |
| A Phenome-wide Association and Mendelian Randomization Study for Alzheimer's Disease: A Prospective Cohort Study of 502,493 Participants From the UK Biobank. | Chen SD et al. | β | 2023 | β |
| Associations between individual depressive symptoms and immunometabolic characteristics in major depression. | Chae WR et al. | β | 2023 | β |
| Characteristics and symptomatology of major depressive disorder with atypical features from symptom to syndromal level. | Shi Y et al. | β | 2023 | β |
| Dissection of depression heterogeneity using proteomic clusters. | van Haeringen M et al. | β | 2023 | β |
| Melancholic features and typical neurovegetative symptoms of major depressive disorder show specific polygenic patterns. | Oliva V et al. | β | 2023 | β |
| Mendelian randomization studies of depression: evidence, opportunities, and challenges. | Ma WR et al. | β | 2023 | β |
| Multimodal Data Integration Advances Longitudinal Prediction of the Naturalistic Course of Depression and Reveals a Multimodal Signature of Remission During 2-Year Follow-up. | Habets PC et al. | β | 2023 | β |
| Sodium-Glucose Cotransporter-2 Inhibitors in Depression. | Liebers DT et al. | β | 2023 | β |
| The association between trauma exposure, polygenic risk and individual depression symptoms. | Thorp JG et al. | β | 2023 | β |
| The interactive association of adverse childhood experiences and polygenic susceptibility with depressive symptoms and chronic inflammation in older adults: a prospective cohort study. | Iob E et al. | β | 2023 | β |
| The interplay of personality traits, anxiety, and depression in Chinese college students: a network analysis. | Yang T et al. | β | 2023 | β |
| Cytokine and Reward Circuitry Relationships in Treatment-Resistant Depression. | Rengasamy M et al. | β | 2022 | β |
| Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption. | Badini I et al. | β | 2022 | β |
| Evolutionarily conserved gene expression patterns for affective disorders revealedΒ using cross-species brain transcriptomic analyses in humans, rats and zebrafish. | Demin KA et al. | β | 2022 | β |
| Genetic heterogeneity and subtypes of major depression. | Nguyen TD et al. | β | 2022 | β |
| Genetic heterogeneity: Challenges, impacts, and methods through an associative lens. | Woodward AA et al. | β | 2022 | β |
| Machine learning, pharmacogenomics, and clinical psychiatry: predicting antidepressant response in patients with major depressive disorder. | Bobo WV et al. | β | 2022 | β |
| Major depressive disorder: a possible typisation according to serotonin, inflammation, and metabolic syndrome. | SiliΔ A et al. | β | 2022 | β |
| Metabolomic and inflammatory signatures of symptom dimensions in major depression. | Brydges CR et al. | β | 2022 | β |
| Mood and anxiety profiles differentially associate with physical conditions in US adolescents. | Stapp EK et al. | β | 2022 | β |
| The Australian Genetics of Depression Study: New Risk Loci and Dissecting Heterogeneity Between Subtypes. | Mitchell BL et al. | β | 2022 | β |
| The gut microbiota and depressive symptoms across ethnic groups. | Bosch JA et al. | β | 2022 | β |
| Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. | Milaneschi Y et al. | β | 2021 | β |
| Associations Between Common Forms of Psychopathology and Fecundity: Evidence From a Prospective, Longitudinal Twin Study. | Wilson S et al. | β | 2021 | β |
| Causal relationships between blood lipids and depression phenotypes: a Mendelian randomisation analysis. | So HC et al. | β | 2021 | β |
| Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity. | Peel AJ et al. | β | 2021 | β |
| Dietary Patterns are Differentially Associated with Atypical and Melancholic Subtypes of Depression. | Lasserre AM et al. | β | 2021 | β |
| Dissecting the Association Between Inflammation, Metabolic Dysregulation, and Specific Depressive Symptoms: A Genetic Correlation and 2-Sample Mendelian Randomization Study. | Kappelmann N et al. | β | 2021 | β |
| Exploring the genetic heterogeneity in major depression across diagnostic criteria. | Jermy BS et al. | β | 2021 | β |
| Factors related to age at depression onset: the role of SLC6A4 methylation, sex, exposure to stressful life events and personality in a sample of inpatients suffering from major depression. | Sanwald S et al. | β | 2021 | β |
| GABAergic polygenic risk for cocaine use disorder is negatively correlated with precuneus activity during cognitive control in African American individuals. | Yang BZ et al. | β | 2021 | β |
| Genetic Overlap Between Alzheimer's Disease and Depression Mapped Onto the Brain. | Monereo-SΓ‘nchez J et al. | β | 2021 | β |
| Is an irritable ADHD profile traceable using personality dimensions? Replicability, stability, and predictive value over time of data-driven profiles. | Blanken TF et al. | β | 2021 | β |
| Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions. | Sen ZD et al. | β | 2021 | β |
| Neuroendocrine Response to Psychosocial Stressors, Inflammation Mediators and Brain-periphery Pathways of Adaptation. | Palego L et al. | β | 2021 | β |
| Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts. | Pistis G et al. | β | 2021 | β |
| Polygenic risk for immuno-metabolic markers and specific depressive symptoms: A multi-sample network analysis study. | Kappelmann N et al. | β | 2021 | β |
| A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. | Shen X et al. | β | 2020 | β |
| Approaches to Defining Common and Dissociable Neurobiological Deficits Associated With Psychopathology in Youth. | Kaczkurkin AN et al. | β | 2020 | β |
| Causes and Consequences of Diagnostic Heterogeneity in Depression: Paths to Discovering Novel Biological Depression Subtypes. | Lynch CJ et al. | β | 2020 | β |
| Characteristics, comorbidities, and correlates of atypical depression: evidence from the UK Biobank Mental Health Survey. | Brailean A et al. | β | 2020 | β |
| Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study. | Corponi F et al. | β | 2020 | β |
| Depression Heterogeneity and Its Biological Underpinnings: Toward Immunometabolic Depression. | Milaneschi Y et al. | β | 2020 | β |
| Genetic stratification of depression in UK Biobank. | Howard DM et al. | β | 2020 | β |
| How to Utilize Clinical and Genetic Information for Personalized Treatment of Major Depressive Disorder: Step by Step Strategic Approach. | Fabbri C et al. | β | 2020 | β |
| Leveraging correlations between variants in polygenic risk scores to detect heterogeneity in GWAS cohorts. | Yuan J et al. | β | 2020 | β |
| Mental health is biological health: Why tackling "diseases of the mind" is an imperative for biological anthropology in the 21st century. | Syme KL et al. | β | 2020 | β |
| Neurovegetative symptom subtypes in young people with major depressive disorder and their structural brain correlates. | Toenders YJ et al. | β | 2020 | β |
| Redefining phenotypes to advance psychiatric genetics: Implications from hierarchical taxonomy of psychopathology. | Waszczuk MA et al. | β | 2020 | β |
| Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies. | Cai N et al. | β | 2020 | β |
| Risk Factors for Adult Depression: Adverse Childhood Experiences and Personality Functioning. | Dagnino P et al. | β | 2020 | β |
| Symptom networks in acute depression across bipolar and major depressive disorders: A network analysis on a large, international, observational study. | Corponi F et al. | β | 2020 | β |
| The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes. | BrΓΌckl TM et al. | β | 2020 | β |
| A role for vitamin D and omega-3 fatty acids in major depression? An exploration using genomics. | Milaneschi Y et al. | β | 2019 | β |
| Cholinergic regulation of mood: from basic and clinical studies to emerging therapeutics. | Dulawa SC et al. | β | 2019 | β |
| Data-driven biological subtypes of depression: systematic review of biological approaches to depression subtyping. | Beijers L et al. | β | 2019 | β |
| Depression and eating styles are independently associated with dietary intake. | Paans NPG et al. | β | 2019 | β |
| Depression and obesity: evidence of shared biological mechanisms. | Milaneschi Y et al. | β | 2019 | β |
| [Genetic comorbidity of depression and somatic disorders]. | Rukavishnikov GV et al. | β | 2019 | β |
| GWAS and Beyond: Using Omics Approaches to Interpret SNP Associations. | Chen HH et al. | β | 2019 | β |
| Health, pre-disease and critical transition to disease in the psycho-immune-neuroendocrine network: Are there distinct states in the progression from health to major depressive disorder? | Stapelberg NJC et al. | β | 2019 | β |
| Increased serum levels of leptin and insulin in both schizophrenia and major depressive disorder: A cross-disorder proteomics analysis. | Γakici N et al. | β | 2019 | β |
| Integration of machine learning and pharmacogenomic biomarkers for predicting response to antidepressant treatment: can computational intelligence be used to augment clinical assessments? | Athreya AP et al. | β | 2019 | β |
| Involvement of inflammatory gene expression pathways in depressed patients with hyperphagia. | de Kluiver H et al. | β | 2019 | β |
| Leveraging correlations between polygenic risk score predictors to detect heterogeneity in GWAS cohorts | Yuan J et al. | β | 2019 | β |
| Progress in psychoradiology, the clinical application of psychiatric neuroimaging. | Huang X et al. | β | 2019 | β |
| Shared pathways for neuroprogression and somatoprogression in neuropsychiatric disorders. | Morris G et al. | β | 2019 | β |
| The association between overall and abdominal adiposity and depressive mood: A cross-sectional analysis in 6459 participants. | Alshehri T et al. | β | 2019 | β |
| The Association Between the Sedative Loads and Clinical Severity Indicators in the First-Onset Major Depressive Disorder. | Wang YC et al. | β | 2019 | β |
| The effect of genetic vulnerability and military deployment on the development of post-traumatic stress disorder and depressive symptoms. | SchΓΌr RR et al. | β | 2019 | β |
| The future of rodent models in depression research. | Gururajan A et al. | β | 2019 | β |
| The Genetics of Treatment-Resistant Depression: A Critical Review and Future Perspectives. | Fabbri C et al. | β | 2019 | β |
| Associations of mindful eating domains with depressive symptoms and depression in three European countries. | Winkens LHH et al. | β | 2018 | β |
| Blood and urinary metabolomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder. | Liu LY et al. | β | 2018 | β |
| Challenges in conducting genetic analyses based on data-driven classification of major depressive disorder. | MΓ€kinen VP | β | 2018 | β |
| Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study. | Pan JX et al. | β | 2018 | β |
| Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. | Peyrot WJ et al. | β | 2018 | β |
| Eating styles in major depressive disorder: Results from a large-scale study. | Paans NPG et al. | β | 2018 | β |
| Effects of genetic deletion versus pharmacological blockade of the LPA<sub>1</sub> receptor on depression-like behaviour and related brain functional activity. | Moreno-FernΓ‘ndez RD et al. | β | 2018 | β |
| Examining neural correlates of psychopathology using a lesion-based approach. | Calamia M et al. | β | 2018 | β |
| Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. | Howard DM et al. | β | 2018 | β |
| Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank. | Hall LS et al. | β | 2018 | β |
| Inflammatory markers and cortisol parameters across depressive subtypes in an older cohort. | Veltman EM et al. | β | 2018 | β |
| Latent class cluster analysis of symptom ratings identifies distinct subgroups within the clinical high risk for psychosis syndrome. | Ryan AT et al. | β | 2018 | β |
| Metabolic and inflammatory markers: associations with individual depressive symptoms. | Lamers F et al. | β | 2018 | β |
| Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications. | Penninx BWJH et al. | β | 2018 | β |
| Molecular Genetic Analysis Subdivided by Adversity Exposure Suggests Etiologic Heterogeneity in Major Depression. | Peterson RE et al. | β | 2018 | β |
| Neurobiological substrates underlying the effect of genomic risk for depression on the conversion of amnestic mild cognitive impairment. | Xu J et al. | β | 2018 | β |
| Novel functional variants at the GWAS-implicated loci might confer risk to major depressive disorder, bipolar affective disorder and schizophrenia. | Bryzgalov LO et al. | β | 2018 | β |
| Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps. | Dick DM et al. | β | 2018 | β |
| Problems with latent class analysis to detect data-driven subtypes of depression. | van Loo HM et al. | β | 2018 | β |
| PRS-on-Spark (PRSoS): a novel, efficient and flexible approach for generating polygenic risk scores. | Chen LM et al. | β | 2018 | β |
| Regulatory T Cells As Supporters of Psychoimmune Resilience: Toward Immunotherapy of Major Depressive Disorder. | Ellul P et al. | β | 2018 | β |
| Robust symptom networks in recurrent major depression across different levels of genetic and environmental risk. | van Loo HM et al. | β | 2018 | β |
| The association between depression and eating styles in four European countries: The MooDFOOD prevention study. | Paans NPG et al. | β | 2018 | β |
| The use of latent class analysis for identifying subtypes of depression: A systematic review. | Ulbricht CM et al. | β | 2018 | β |
| The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression: A systematic review. | Mistry S et al. | β | 2018 | β |
| The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: Systematic review. | Mistry S et al. | β | 2018 | β |
| Transdiagnostic Symptom Clusters and Associations With Brain, Behavior, and Daily Function in Mood, Anxiety, and Trauma Disorders. | Grisanzio KA et al. | β | 2018 | β |
| Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data. | Gibson J et al. | β | 2017 | β |
| Common genes associated with antidepressant response in mouse and man identify key role of glucocorticoid receptor sensitivity. | Carrillo-Roa T et al. | β | 2017 | β |
| Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders. | Xiao X et al. | β | 2017 | β |
| Comorbidities in the diseasome are more apparent than real: What Bayesian filtering reveals about the comorbidities of depression. | Marx P et al. | β | 2017 | β |
| Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms. | Penninx BW | β | 2017 | β |
| Depressive subtypes in an elderly cohort identified using latent class analysis. | Veltman EM et al. | β | 2017 | β |
| Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations. | Milaneschi Y et al. | β | 2017 | β |
| Genetics of Depression: Progress at Last. | Mullins N et al. | β | 2017 | β |
| Genome-wide Regional Heritability Mapping Identifies a Locus Within the TOX2 Gene Associated With Major Depressive Disorder. | Zeng Y et al. | β | 2017 | β |
| Is a polygenic predictor of antidepressant response a possibility? | Fabbri C | β | 2017 | β |
| Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression. | Milaneschi Y et al. | β | 2017 | β |
| Role of Neuro-Immunological Factors in the Pathophysiology of Mood Disorders: Implications for Novel Therapeutics for Treatment Resistant Depression. | Bhattacharya A et al. | β | 2017 | β |
| The association of childhood maltreatment with depression and anxiety is not moderated by the oxytocin receptor gene. | Tollenaar MS et al. | β | 2017 | β |
| Using Clinical Characteristics to Identify Which Patients With Major Depressive Disorder Have a Higher Genetic Load for Three Psychiatric Disorders. | Verduijn J et al. | β | 2017 | β |
| Validity of LIDAS (LIfetime Depression Assessment Self-report): a self-report online assessment of lifetime major depressive disorder. | Bot M et al. | β | 2017 | β |
| Beyond Lumping and Splitting: A Review of Computational Approaches for Stratifying Psychiatric Disorders. | Marquand AF et al. | β | 2016 | β |
| Dissection of major depressive disorder using polygenic risk scores for schizophrenia in two independent cohorts. | Whalley HC et al. | β | 2016 | β |
| Genetic Epidemiology and Public Health: The Evolution From Theory to Technology. | Fallin MD et al. | β | 2016 | β |
| Serum proteomic profiles of depressive subtypes. | Lamers F et al. | β | 2016 | β |
| The mediation effect of emotional eating between depression and body mass index in the two European countries Denmark and Spain. | van Strien T et al. | β | 2016 | β |