ArticleTranslational psychiatry2013
Multiple variants aggregate in the neuregulin signaling pathway in a subset of schizophrenia patients.
Article in Translational psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Integrative multi-omics and machine learning analysis identifies candidate biomarkers associated with mitochondrial quality control in major depressive disorder.Frontiers in psychiatry · 2026Article
- Genetic Influences on Cognitive Dysfunction in Schizophrenia.Current topics in behavioral neurosciences · 2023Article
- Age-specific impacts of nicotine and withdrawal on hippocampal neuregulin signalling.The European journal of neuroscience · 2022Article
- Repeated Winning and Losing Experiences in Chronic Social Conflicts Are Linked to RNA Editing Pattern Difference.Frontiers in psychiatry · 2022Article
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Genome-wide Association of Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia (COGS) Study.JAMA psychiatry · 2019Article
- Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons.The EMBO journal · 2018Article
- Neuregulin 3 and its roles in schizophrenia risk and presentation.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2018Review
- Article
- Neuregulin signaling pathway in smoking behavior.Translational psychiatry · 2017Article
- Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder.Scientific reports · 2017Article
- Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations.Translational psychiatry · 2017Article
- Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons.Cell reports · 2017Article
- Neuregulin 3 Knockout Mice Exhibit Behaviors Consistent with Psychotic Disorders.Molecular neuropsychiatry · 2016Article
- Bridging the Gap between Genes and Language Deficits in Schizophrenia: An Oscillopathic Approach.Frontiers in human neuroscience · 2016Article
- Physiological and behavioral effects of amphetamine in BACE1(-/-) mice.Genes, brain, and behavior · 2015Article
- Identification and functional studies of regulatory variants responsible for the association ofMolecular neuropsychiatry · 2015Article
- ERBB4 polymorphism and family history of psychiatric disorders on age-related cortical changes in healthy children.Brain imaging and behavior · 2015Article
- Recent genetic findings in schizophrenia and their therapeutic relevance.Journal of psychopharmacology (Oxford, England) · 2015Review
- Role of the Neuregulin Signaling Pathway in Nicotine Dependence and Co-morbid Disorders.International review of neurobiology · 2015Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Despite the strongly held view that schizophrenia (SZ) shows substantial genetic heterogeneity, pathway heterogeneity, as seen in cancer where different pathways are affected in similar tumors, has not been explored. We explore this possibility in a case-only study of the neuregulin signaling pathway (NSP), which has been prominently implicated in SZ and for which there is detailed knowledge on the ligand- and receptor-processing steps through β- and γ-secretase cleavage. We hypothesize that more than one damaging variants in the NSP genes might be necessary to cause disease, leading to an apparent clustering of such variants in only the few patients with affected NSP. We analyze linkage and next-generation sequencing results for the genes encoding components of the pathway, including NRG1, NRG3, ERBB4, β-secretase and the γ-secretase complex. We find multiple independent examples of supporting evidence for this hypothesis: (i) increased linkage scores over NSP genes, (ii) multiple positive interlocus correlations of linkage scores across families suggesting each family is linked to either many or none of the genes, (iii) aggregation of predicted damaging variants in a subset of individuals and (iv) significant phenotypic differences of the subset of patients carrying such variants. Collectively, our data strongly support the hypothesis that the NSP is affected by multiple damaging variants in a subset of phenotypically distinct patients. On the basis of this, we propose a general model of pathway heterogeneity in SZ, which, in part, may explain its phenotypic variability and genetic complexity.
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