ArticleG3 (Bethesda, Md.)2014
Functional variants in DPYSL2 sequence increase risk of schizophrenia and suggest a link to mTOR signaling.
Article in G3 (Bethesda, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Exploring the roots of schizophrenia: Current research and future directions (Review).Experimental and therapeutic medicine · 2026Review
- Translational bioinformatics and data science for biomarker discovery in mental health: an analytical review.Briefings in bioinformatics · 2024Review
- Overlap in synaptic neurological condition susceptibility pathways and the neural pannexin 1 interactome revealed by bioinformatics analyses.Channels (Austin, Tex.) · 2023Article
- DPYSL2/CRMP2 isoform B knockout in human iPSC-derived glutamatergic neurons confirms its role in mTOR signaling and neurodevelopmental disorders.Molecular psychiatry · 2023Article
- Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability.Molecular psychiatry · 2022Article
- Article
- Cellular Models in Schizophrenia Research.International journal of molecular sciences · 2021Review
- Discovering the Lost Reward: Critical Locations for Endocannabinoid Modulation of the Cortico-Striatal Loop That Are Implicated in Major Depression.International journal of molecular sciences · 2021Review
- Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice.Scientific reports · 2020Article
- CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling.EMBO reports · 2020Article
- Dysregulation of CRMP2 Post-Translational Modifications Drive Its Pathological Functions.Molecular neurobiology · 2019Review
- Enhanced carbonyl stress induces irreversible multimerization of CRMP2 in schizophrenia pathogenesis.Life science alliance · 2019Article
- Review
- mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders.International journal of molecular sciences · 2018Review
- Recent Advances in the Genetics of Schizophrenia.Molecular neuropsychiatry · 2018Review
- Phytocannabinoids modulate emotional memory processing through interactions with the ventral hippocampus and mesolimbic dopamine system: implications for neuropsychiatric pathology.Psychopharmacology · 2018Review
- PI3K-mTOR-S6K Signaling Mediates Neuronal Viability via Collapsin Response Mediator Protein-2 Expression.Frontiers in molecular neuroscience · 2017Article
- The DPYSL2 gene connects mTOR and schizophrenia.Translational psychiatry · 2016Article
- A novel mouse model for the identification of thioredoxin-1 protein interactions.Free radical biology & medicine · 2016Article
- Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.Nature communications · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Numerous linkage and association studies by our group and others have implicated DPYSL2 at 8p21.2 in schizophrenia. Here we explore DPYSL2 for functional variation that underlies these associations. We sequenced all 14 exons of DPYSL2 as well as 27 conserved noncoding regions at the locus in 137 cases and 151 controls. We identified 120 variants, eight of which we genotyped in an additional 729 cases and 1542 controls. Several were significantly associated with schizophrenia, including a three single-nucleotide polymorphism (SNP) haplotype in the proximal promoter, two SNPs in intron 1, and a polymorphic dinucleotide repeat in the 5'-untranslated region that alters sequences predicted to be involved in translational regulation by mammalian target of rapamycin signaling. The 3-SNP promoter haplotype and the sequence surrounding one of the intron 1 SNPs direct tissue-specific expression in the nervous systems of Zebrafish in a pattern consistent with the two endogenous dpysl2 paralogs. In addition, two SNP haplotypes over the coding exons and 3' end of DPYSL2 showed association with opposing sex-specific risks. These data suggest that these polymorphic, schizophrenia-associated sequences function as regulatory elements for DPYSL2 expression. In transient transfection assays, the high risk allele of the polymorphic dinucleotide repeat diminished reporter expression by 3- to 4-fold. Both the high- and low-risk alleles respond to allosteric mTOR inhibition by rapamycin until, at high drug levels, allelic differences are eliminated. Our results suggest that reduced transcription and mTOR-regulated translation of certain DPYSL2 isoforms increase the risk for schizophrenia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.