ArticleTranslational psychiatry2012
Schizophrenia-associated HapICE haplotype is associated with increased NRG1 type III expression and high nucleotide diversity.
Article in Translational psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- A systematic meta-analysis of the association of Neuregulin 1 (NRG1), D-amino acid oxidase (DAO), and DAO activator (DAOA)/G72 polymorphisms with schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2018Pooled it
- Drug Repurposing for Treating NCOR-Related Intellectual Disability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antagonizing NRG1-ERBB4 signaling pathway with spironolactone for the treatment of schizophrenia: results of a randomized controlled drug repositioning clinical trial.Communications medicine · 2026Article
- A Novel Form of Neuregulin 1 Type III Caused by N-Terminal Processing.Biomolecules · 2023Article
- The genetic basis of onset age in schizophrenia: evidence and models.Frontiers in genetics · 2023Review
- Gene Polymorphisms and Expression ofNeuropsychiatric disease and treatment · 2023Article
- Neurobehavioral Profiles of Six Genetically-based Rat Models of Schizophrenia- related Symptoms.Current neuropharmacology · 2023Article
- Overexpression of Neuregulin-1 Type III Has Impact on Visual Function in Mice.International journal of molecular sciences · 2022Article
- An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data.Molecular psychiatry · 2022Review
- Efficacy of Spironolactone as an Adjunctive Therapy to Risperidone to Improve Symptoms of Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled, Clinical Trial.Iranian journal of psychiatry · 2022Article
- Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition.Nature communications · 2021Article
- Neuregulin 1: an intriguing therapeutic target for neurodevelopmental disorders.Translational psychiatry · 2020Review
- Add-on spironolactone as antagonist of the NRG1-ERBB4 signaling pathway for the treatment of schizophrenia: Study design and methodology of a multicenter randomized, placebo-controlled trial.Contemporary clinical trials communications · 2020Article
- Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy.Human molecular genetics · 2019Article
- Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I.Translational psychiatry · 2018Article
- A Novel Ultrasensitive In Situ Hybridization Approach to Detect Short Sequences and Splice Variants with Cellular Resolution.Molecular neurobiology · 2018Article
- Overexpression of Neuregulin 1 Type III Confers Hippocampal mRNA Alterations and Schizophrenia-Like Behaviors in Mice.Schizophrenia bulletin · 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
- Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients.Translational psychiatry · 2017Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excitement and controversy have followed neuregulin (NRG1) since its discovery as a putative schizophrenia susceptibility gene; however, the mechanism of action of the associated risk haplotype (HapICE) has not been identified, and specific genetic variations, which may increase risk to schizophrenia have remained elusive. Using a postmortem brain cohort from 37 schizophrenia cases and 37 controls, we resequenced upstream of the type I-IV promoters, and the HapICE repeat regions in intron 1. Relative abundance of seven NRG1 mRNA transcripts in the prefrontal cortex were determined and compared across diagnostic and genotypic groups. We identified 26 novel DNA variants and showed an increased novel variant load in cases compared with controls (χ(2)=7.815; P=0.05). The average nucleotide diversity (θ = 10.0 × 10(-4)) was approximately twofold higher than that previously reported for BDNF, indicating that NRG1 may be particularly prone to genetic change. A greater nucleotide diversity was observed in the HapICE linkage disequilibrium block in schizophrenia cases (θ((case)) = 13.2 × 10(-4); θ((control)) = 10.0 × 10(-4)). The specific HapICE risk haplotype was associated with increased type III mRNA (F = 3.76, P = 0.028), which in turn, was correlated with an earlier age of onset (r = -0.343, P = 0.038). We found a novel intronic five-SNP haplotype ~730 kb upstream of the type I promoter and determined that this region functions as transcriptional enhancer that is suppressed by SRY. We propose that the HapICE risk haplotype increases expression of the most brain-abundant form of NRG1, which in turn, elicits an earlier clinical presentation, thus providing a novel mechanism through which this genetic association may increase risk of schizophrenia.
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