ArticleProceedings of the National Academy of Sciences of the United States of America2008
A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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.
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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
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis.Molecular psychiatry · 2025Pooled it
- Neurophysiological profiles of patients with bipolar disorders as probed with transcranial magnetic stimulation: A systematic review.Neuropsychopharmacology reports · 2024Pooled it
- Structural insights into kainate receptor desensitization.Nature communications · 2025Article
- Central role of regular firing neurons of centrolateral amygdala in affective behaviors.iScience · 2025Article
- Article
- Codes between Poles: Linking Transcriptomic Insights into the Neurobiology of Bipolar Disorder.Biology · 2024Article
- Structure, Function, and Regulation of the Kainate Receptor.Sub-cellular biochemistry · 2022Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Prediction of lithium response using genomic data.Scientific reports · 2021Article
- The Coordination of Local Translation, Membranous Organelle Trafficking, and Synaptic Plasticity in Neurons.Frontiers in cell and developmental biology · 2021Review
- Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities.Scientific reports · 2019Article
- Kainate Receptors Inhibit Glutamate Release Via Mobilization of Endocannabinoids in Striatal Direct Pathway Spiny Projection Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Framework for reanalysis of publicly available Affymetrix® GeneChip® data sets based on functional regions of interest.BMC genomics · 2017Article
- Genetic Studies on the Tripartite Glutamate Synapse in the Pathophysiology and Therapeutics of Mood Disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Review
- Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice.Cell reports · 2017Article
- Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders.Neural plasticity · 2017Review
- Increased Dosage of High-Affinity Kainate Receptor Gene grik4 Alters Synaptic Transmission and Reproduces Autism Spectrum Disorders Features.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Characterization of a Novel Mutation in SLC1A1 Associated with Schizophrenia.Molecular neuropsychiatry · 2015Article
- Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.Molecular pharmacology · 2015Review
- Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3' end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3' untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression.
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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.