Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression.
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- Authors
- Rietschel, Marcella; Mattheisen, Manuel; Frank, Josef; Treutlein, Jens; Degenhardt, Franziska; Breuer, René; Steffens, Michael; Mier, Daniela; Esslinger, Christine; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Schnell, Knut; Herms, Stefan; Wichmann, H-Erich; Schreiber, Stefan; Jöckel, Karl-Heinz; Strohmaier, Jana; Roeske, Darina; Haenisch, Britta; Gross, Magdalena; Hoefels, Susanne; Lucae, Susanne; Binder, Elisabeth B; Wienker, Thomas F; Schulze, Thomas G; Schmäl, Christine; Zimmer, Andreas; Juraeva, Dilafruz; Brors, Benedikt; Bettecken, Thomas; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Maier, Wolfgang; Nöthen, Markus M; Cichon, Sven
- Year
- 2010
- Journal
- Biological psychiatry
- PMID
- 20673876
- DOI
- 10.1016/j.biopsych.2010.05.038
BACKGROUND: Genome-wide association studies are a powerful tool for unravelling the genetic background of complex disorders such as major depression. METHODS: We conducted a genome-wide association study of 604 patients with major depression and 1364 population based control subjects. The top hundred findings were followed up in a replication sample of 409 patients and 541 control subjects. RESULTS: Two SNPs showed nominally significant association in both the genome-wide association study and the replication samples: 1) rs9943849 (p(combined) = 3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917 (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1. Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1 knockout mice display behavioral traits that are paradigmatic of depression, and transcriptional variants of Homer1 result in the dysregulation of cortical-limbic circuitry. This is consistent with the findings of our subsequent human imaging genetics study, which revealed that variation in single nucleotide polymorphism rs7713917 had a significant influence on prefrontal activity during executive cognition and anticipation of reward. CONCLUSION: Our findings, combined with evidence from preclinical and animal studies, suggest that HOMER1 plays a role in the etiology of major depression and that the genetic variation affects depression via the dysregulation of cognitive and motivational processes.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Optimization of potential targets for antidepressant Chinese medicines: AI and multi-omics methods. | Lei C et al. | — | 2026 | → |
| Identification and validation of depression-associated genetic variants in the UK Biobank cohort with transcriptome and DNA methylation analyses in independent cohorts. | Lafta MS et al. | — | 2025 | → |
| Transcriptomic Insights into Late-Life Depression and the Role of Environmental Drinking Water Composition: A Study on 18-Month-Old Mice. | Costa-Nunes JP et al. | — | 2025 | → |
| Aberrant encoding of event saliency in the orbitofrontal cortex following loss of the psychiatric-associated circular RNA, circHomer1. | Zimmerman AJ et al. | — | 2024 | → |
| A single 24 h maternal separation at PND 9 promotes behavioral resilience of female C57BL/6J mice and the possible role of hippocampal Homer1a. | Hao Y et al. | — | 2024 | → |
| Association between handgrip strength and depressive symptoms in patients undergoing hemodialysis: a cross-sectional study from a single Chinese center. | Zhang S et al. | — | 2024 | → |
| Interactions of the CSF3R polymorphism and early stress on future orientation: evidence for the differential model of stress-related growth. | Gan Y et al. | — | 2024 | → |
| Multimodal integration of neuroimaging and genetic data for the diagnosis of mood disorders based on computer vision models. | Lee S et al. | — | 2024 | → |
| Dysregulated Signaling at Postsynaptic Density: A Systematic Review and Translational Appraisal for the Pathophysiology, Clinics, and Antipsychotics' Treatment of Schizophrenia. | de Bartolomeis A et al. | — | 2023 | → |
| Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers. | Singh P et al. | — | 2023 | → |
| The genetic basis of major depressive disorder. | Flint J | — | 2023 | → |
| The Neurobiological Underpinnings of Obsessive-Compulsive Symptoms in Psychosis, Translational Issues for Treatment-Resistant Schizophrenia. | Vellucci L et al. | — | 2023 | → |
| Adenosine, caffeine, and sleep-wake regulation: state of the science and perspectives. | Reichert CF et al. | — | 2022 | → |
| Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals. | Anguita-Ruiz A et al. | — | 2022 | → |
| Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings. | Li M et al. | — | 2022 | → |
| Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress. | Liu CY et al. | — | 2022 | → |
| The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight. | de Bartolomeis A et al. | — | 2022 | → |
| Update on GPCR-based targets for the development of novel antidepressants. | Mantas I et al. | — | 2022 | → |
| Antidepressant treatment is associated with epigenetic alterations of Homer1 promoter in a mouse model of chronic depression. | Sun L et al. | — | 2021 | → |
| Frontal cortex genetic ablation of metabotropic glutamate receptor subtype 3 (mGlu<sub>3</sub>) impairs postsynaptic plasticity and modulates affective behaviors. | Joffe ME et al. | — | 2021 | → |
| Genetic neuroimaging of bipolar disorder: a systematic 2017-2020 update. | Janiri D et al. | — | 2021 | → |
| Lack of association of FKBP5 SNPs and haplotypes with susceptibility and treatment response phenotypes in Han Chinese with major depressive disorder: A pilot case-control study (STROBE). | Yang C et al. | — | 2021 | → |
| Rare Pathogenic Variants in Genes Implicated in Glutamatergic Neurotransmission Pathway Segregate with Schizophrenia in Pakistani Families. | Fatima A et al. | — | 2021 | → |
| Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: An impact of early-life stress. | Reshetnikov VV et al. | — | 2021 | → |
| The genetic basis of major depression. | Kendall KM et al. | — | 2021 | → |
| The role of rs242941, rs1876828, rs242939 and rs110402 polymorphisms of CRHR1 gene and the depression: systematic review and meta-analysis. | Hernández-Díaz Y et al. | — | 2021 | → |
| The Role of Stress-Induced Changes of Homer1 Expression in Stress Susceptibility. | Reshetnikov VV et al. | — | 2021 | → |
| A joint study of whole exome sequencing and structural MRI analysis in major depressive disorder. | Zhang Y et al. | — | 2020 | → |
| CHIMGEN: a Chinese imaging genetics cohort to enhance cross-ethnic and cross-geographic brain research. | Xu Q et al. | — | 2020 | → |
| DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning. | Arloth J et al. | — | 2020 | → |
| Distinct and Overlapping Expression Patterns of the Homer Family of Scaffolding Proteins and Their Encoding Genes in Developing Murine Cephalic Tissues. | Reibring CG et al. | — | 2020 | → |
| Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects. | Rantamäki T et al. | — | 2020 | → |
| Genomic analyses reveal distinct genetic architectures and selective pressures in buffaloes. | Sun T et al. | — | 2020 | → |
| Interactions of childhood maltreatment and genetic variations in adult depression: A systematic review. | Li M et al. | — | 2020 | → |
| Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms. | Thomas M et al. | — | 2020 | → |
| [Breakthrough in understanding the molecular causes of psychiatric disorders]. | Nöthen MM et al. | — | 2019 | → |
| Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. | Lai D et al. | — | 2019 | → |
| GWAS of Behavioral Traits. | Mehta D et al. | — | 2019 | → |
| Integration of GWAS and brain eQTL identifies FLOT1 as a risk gene for major depressive disorder. | Zhong J et al. | — | 2019 | → |
| Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder. | Li H et al. | — | 2019 | → |
| Recommendations on Collecting and Storing Samples for Genetic Studies in Hearing and Tinnitus Research. | Szczepek AJ et al. | — | 2019 | → |
| Regulation and Function of Activity-Dependent Homer in Synaptic Plasticity. | Clifton NE et al. | — | 2019 | → |
| Systems Approach to Identify Common Genes and Pathways Associated with Response to Selective Serotonin Reuptake Inhibitors and Major Depression Risk. | Srivastava A et al. | — | 2019 | → |
| A Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: A multimodal genetic imaging study. | Benedetti F et al. | — | 2018 | → |
| Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition. | Lang D et al. | — | 2018 | → |
| Genetics Factors in Major Depression Disease. | Shadrina M et al. | — | 2018 | → |
| Molecular genetic overlap between migraine and major depressive disorder. | Yang Y et al. | — | 2018 | → |
| Neuroimaging genomic studies in major depressive disorder: A systematic review. | Zhang HF et al. | — | 2018 | → |
| Recent insights into antidepressant therapy: Distinct pathways and potential common mechanisms in the treatment of depressive syndromes. | van Calker D et al. | — | 2018 | → |
| Shared genetic etiology between alcohol dependence and major depressive disorder. | Foo JC et al. | — | 2018 | → |
| Synapse development organized by neuronal activity-regulated immediate-early genes. | Kim S et al. | — | 2018 | → |
| The Gene Encoding Protocadherin 9 (PCDH9), a Novel Risk Factor for Major Depressive Disorder. | Xiao X et al. | — | 2018 | → |
| A continuum of genetic liability for minor and major depression. | Corfield EC et al. | — | 2017 | → |
| An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. | Direk N et al. | — | 2017 | → |
| Association between neuropeptide Y receptor Y2 promoter variant rs6857715 and major depressive disorder. | Treutlein J et al. | — | 2017 | → |
| Behavioral and Neurochemical Phenotyping of Mice Incapable of Homer1a Induction. | Datko MC et al. | — | 2017 | → |
| Expert and self-assessment of lifetime symptoms and diagnosis of major depressive disorder in large-scale genetic studies in the general population: comparison of a clinical interview and a self-administered checklist. | Martin J et al. | — | 2017 | → |
| Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. | Power RA et al. | — | 2017 | → |
| Hippocampal Regulation of Postsynaptic Density Homer1 by Associative Learning. | Clifton NE et al. | — | 2017 | → |
| Homer1a protein expression in schizophrenia, bipolar disorder, and major depression. | Leber SL et al. | — | 2017 | → |
| Impaired retention of depression-like behavior in a mouse model of Alzheimer's disease. | Luo X et al. | — | 2017 | → |
| Intergenic variants may predispose to major depression disorder through regulation of long non-coding RNA expression. | Ye N et al. | — | 2017 | → |
| Noncoding RNAs in Depression. | Lin R et al. | — | 2017 | → |
| Resequencing three candidate genes discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese. | Rao S et al. | — | 2017 | → |
| Reward Network Immediate Early Gene Expression in Mood Disorders. | Manning CE et al. | — | 2017 | → |
| Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions. | Tomasetti C et al. | — | 2017 | → |
| Vitamin D and Depression: Cellular and Regulatory Mechanisms. | Berridge MJ | — | 2017 | → |
| Association of HOMER1 rs2290639 with suicide attempts in Hong Kong Chinese and the potentially functional role of this polymorphism. | Rao S et al. | — | 2016 | → |
| Common variants in FKBP5 gene and major depressive disorder (MDD) susceptibility: a comprehensive meta-analysis. | Rao S et al. | — | 2016 | → |
| DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning | Arloth J et al. | — | 2016 | — |
| Does refining the phenotype improve replication rates? A review and replication of candidate gene studies on Major Depressive Disorder and Chronic Major Depressive Disorder. | Luo X et al. | — | 2016 | → |
| Genome-wide linkage on chromosome 10q26 for a dimensional scale of major depression. | Knowles EE et al. | — | 2016 | → |
| Identification of SLC25A37 as a major depressive disorder risk gene. | Huo YX et al. | — | 2016 | → |
| Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender. | Klein M et al. | — | 2016 | → |
| Morc1 knockout evokes a depression-like phenotype in mice. | Schmidt M et al. | — | 2016 | → |
| Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity. | Heinrich A et al. | — | 2016 | → |
| Protein biomarkers of susceptibility and resilience to stress in a rat model of depression. | Palmfeldt J et al. | — | 2016 | → |
| Pushing the threshold: How NMDAR antagonists induce homeostasis through protein synthesis to remedy depression. | Raab-Graham KF et al. | — | 2016 | → |
| Recurrent major depression and right hippocampal volume: A bivariate linkage and association study. | Mathias SR et al. | — | 2016 | → |
| A glutamatergic network mediates lithium response in bipolar disorder as defined by epigenome pathway analysis. | Higgins GA et al. | — | 2015 | → |
| Alteration by p11 of mGluR5 localization regulates depression-like behaviors. | Lee KW et al. | — | 2015 | → |
| Comparative genome-wide association studies of a depressive symptom phenotype in a repeated measures setting by race/ethnicity in the Multi-Ethnic Study of Atherosclerosis. | Ware EB et al. | — | 2015 | → |
| Epidemiological support for genetic variability at hypothalamic-pituitary-adrenal axis and serotonergic system as risk factors for major depression. | Ching-López A et al. | — | 2015 | → |
| Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. | Ferentinos P et al. | — | 2015 | → |
| FRAS1-related extracellular matrix 3 (FREM3) single-nucleotide polymorphism effects on gene expression, amygdala reactivity and perceptual processing speed: An accelerated aging pathway of depression risk. | Nikolova YS et al. | — | 2015 | → |
| Functional characterization of the PCLO p.Ser4814Ala variant associated with major depressive disorder reveals cellular but not behavioral differences. | Giniatullina A et al. | — | 2015 | → |
| Genetic determinants of depression: recent findings and future directions. | Dunn EC et al. | — | 2015 | → |
| Homer1a-dependent recovery from depression-like behavior by photic stimulation in mice. | Sun P et al. | — | 2015 | → |
| Homer1a disruption increases vulnerability to predictable subtle stress normally sub-threshold for behavioral changes. | Shui Y et al. | — | 2015 | → |
| Homer1/mGluR5 activity moderates vulnerability to chronic social stress. | Wagner KV et al. | — | 2015 | → |
| Increased Signaling via Adenosine A1 Receptors, Sleep Deprivation, Imipramine, and Ketamine Inhibit Depressive-like Behavior via Induction of Homer1a. | Serchov T et al. | — | 2015 | → |
| Inhibition of Attention for Affective Material: Contributions by <i>HOMER1</i> Gene Variation. | Wells TT et al. | — | 2015 | → |
| Insight in genome-wide association of metabolite quantitative traits by exome sequence analyses. | Demirkan A et al. | — | 2015 | → |
| Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis. | Musliner KL et al. | — | 2015 | → |
| Potential roles for Homer1 and Spinophilin in the preventive effect of electroconvulsive seizures on stress-induced CA3c dendritic retraction in the hippocampus. | Kaastrup Müller H et al. | — | 2015 | → |
| The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects. | Peyrot WJ et al. | — | 2015 | → |
| A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies. | Chang LC et al. | — | 2014 | → |
| A recessive genetic model and runs of homozygosity in major depressive disorder. | Power RA et al. | — | 2014 | → |
| Association of HTR2A T102C and A-1438G polymorphisms with susceptibility to major depressive disorder: a meta-analysis. | Zhao X et al. | — | 2014 | → |
| Bipolar polygenic loading and bipolar spectrum features in major depressive disorder. | Wiste A et al. | — | 2014 | → |
| Epistatic interaction of genetic depression risk variants in the human subgenual cingulate cortex during memory encoding. | Schott BH et al. | — | 2014 | → |
| Etiological heterogeneity of symptom dimensions of adolescent depression. | Chen J et al. | — | 2014 | → |
| Genetic variants in the genes of the stress hormone signalling pathway and depressive symptoms during and after pregnancy. | Schneider M et al. | — | 2014 | → |
| Genetic variation in CACNA1C affects neural processing in major depression. | Backes H et al. | — | 2014 | → |
| Hippocampal Homer1 levels influence motivational behavior in an operant conditioning task. | Wagner KV et al. | — | 2014 | → |
| Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder. | Leuchter AF et al. | — | 2014 | → |
| Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution. | Ferentinos P et al. | — | 2014 | → |
| MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD. | Nieratschker V et al. | — | 2014 | → |
| Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course? | Wilson S et al. | — | 2014 | → |
| Rethinking metabotropic glutamate receptor 5 pathological findings in psychiatric disorders: implications for the future of novel therapeutics. | Newell KA et al. | — | 2014 | → |
| The emerging role of dopamine-glutamate interaction and of the postsynaptic density in bipolar disorder pathophysiology: Implications for treatment. | de Bartolomeis A et al. | — | 2014 | → |
| The genetics of major depression. | Flint J et al. | — | 2014 | → |
| A genome-wide association study of depressive symptoms. | Hek K et al. | — | 2013 | → |
| A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction. | Deo AJ et al. | — | 2013 | → |
| A mega-analysis of genome-wide association studies for major depressive disorder. | Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium et al. | — | 2013 | → |
| FMR1, circadian genes and depression: suggestive associations or false discovery? | Kripke DF et al. | — | 2013 | → |
| Genome-wide association data provide further support for an association between 5-HTTLPR and major depressive disorder. | Haenisch B et al. | — | 2013 | → |
| Homer1 mediates acute stress-induced cognitive deficits in the dorsal hippocampus. | Wagner KV et al. | — | 2013 | → |
| Implications of the use of genetic tests in psychiatry, with a focus on major depressive disorder: a review. | Wilde A et al. | — | 2013 | → |
| Selected rapporteur summaries from the XX World Congress of Psychiatric Genetics, Hamburg, Germany, October 14-18, 2012. | Anderson-Schmidt H et al. | — | 2013 | → |
| The current state of play on the molecular genetics of depression. | Cohen-Woods S et al. | — | 2013 | → |
| The genetics of alcohol dependence. | Rietschel M et al. | — | 2013 | → |
| The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression. | Samaan Z et al. | — | 2013 | → |
| Toward an integration of cognitive and genetic models of risk for depression. | Gibb BE et al. | — | 2013 | → |
| Association between copy number variants in 16p11.2 and major depressive disorder in a German case-control sample. | Degenhardt F et al. | — | 2012 | → |
| Association study of early-immediate genes in childhood-onset mood disorders and suicide attempt. | Strauss J et al. | — | 2012 | → |
| Behavioral genetics of affective and anxiety disorders. | Domschke K et al. | — | 2012 | → |
| Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate receptor. | de Bartolomeis A et al. | — | 2012 | → |
| Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses. | Visscher PM et al. | — | 2012 | → |
| Functional consequences of mutations in postsynaptic scaffolding proteins and relevance to psychiatric disorders. | Ting JT et al. | — | 2012 | → |
| Genome-wide association study of comorbid depressive syndrome and alcohol dependence. | Edwards AC et al. | — | 2012 | → |
| Genomic structural variation in psychiatric disorders. | Rucker JJ et al. | — | 2012 | → |
| Meta-analysis and brain imaging data support the involvement of VRK2 (rs2312147) in schizophrenia susceptibility. | Li M et al. | — | 2012 | → |
| MicroRNAs and depression. | Mouillet-Richard S et al. | — | 2012 | → |
| MK4MDD: a multi-level knowledge base and analysis platform for major depressive disorder. | Guo L et al. | — | 2012 | → |
| Multi-locus genome-wide association analysis supports the role of glutamatergic synaptic transmission in the etiology of major depressive disorder. | Lee PH et al. | — | 2012 | → |
| Studies in humans and mice implicate neurocan in the etiology of mania. | Miró X et al. | — | 2012 | → |
| The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse. | Jacobsen JP et al. | — | 2012 | → |
| The future of fMRI and genetics research. | Meyer-Lindenberg A | — | 2012 | → |
| A new lead from genetic studies in depressed siblings: assessing studies of chromosome 3. | Hamilton SP | — | 2011 | → |
| Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study. | Sun P et al. | — | 2011 | → |
| Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders. | Mao P | — | 2011 | → |
| The neuronal transporter gene SLC6A15 confers risk to major depression. | Kohli MA et al. | — | 2011 | → |
| The relationship of deiodinase 1 genotype and thyroid function to lifetime history of major depression in three independent populations. | Philibert RA et al. | — | 2011 | → |