ArticleAmerican journal of human genetics2012
Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
- Exome sequencing and metabolite profiling identifies genetic variants associated with altered metabolism in early-onset schizophrenia.iScience · 2026Article
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- RhoGEF Tiam2 Regulates Glutamatergic Synaptic Transmission in Hippocampal CA1 Pyramidal Neurons.eNeuro · 2024Article
- De Novo Variants Found in Three Distinct Schizophrenia Populations Hit a Common Core Gene Network Related to Microtubule and Actin Cytoskeleton Gene Ontology Classes.Life (Basel, Switzerland) · 2024Article
- High-impact rare genetic variants in severe schizophrenia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Endophenotypes in Schizophrenia: Digging Deeper to Identify Genetic Mechanisms.Journal of psychiatry and brain science · 2019Article
- Excess Glutamate May Cause Dilation of Retinal Blood Vessels in Glutamate/Aspartate Transporter-Deficient Mice.BioMed research international · 2019Article
- A novel homozygous mutation in GAD1 gene described in a schizophrenic patient impairs activity and dimerization of GAD67 enzyme.Scientific reports · 2018Article
- Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples.European archives of psychiatry and clinical neuroscience · 2018Article
- Recent Advances in the Genetics of Schizophrenia.Molecular neuropsychiatry · 2018Review
- Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective.Biological psychiatry · 2017Review
- Functional analysis of rare variants found in schizophrenia implicates a critical role for GIT1-PAK3 signaling in neuroplasticity.Molecular psychiatry · 2017Article
- Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future.Progress in neuro-psychopharmacology & biological psychiatry · 2017Review
- Impact of genotyping errors on statistical power of association tests in genomic analyses: A case study.Genetic epidemiology · 2017Article
- The Role of Metabotropic Glutamate Receptor Genes in Schizophrenia.Current neuropharmacology · 2016Review
- Cancer classification in the genomic era: five contemporary problems.Human genomics · 2015Review
- Functional and Structural Consequence of Rare Exonic Single Nucleotide Polymorphisms: One Story, Two Tales.Genome biology and evolution · 2015Article
- Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome.G3 (Bethesda, Md.) · 2015Article
- Copy number variable microRNAs in schizophrenia and their neurodevelopmental gene targets.Biological psychiatry · 2015Article
- Genetics of complex traits in psychiatry.Biological psychiatry · 2015Review
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
Abstract
Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors.
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