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Record W4280590561 · doi:10.1038/s41380-022-01575-x

Genome-wide tandem repeat expansions contribute to schizophrenia risk

2022· article· en· W4280590561 on OpenAlexafffund
Bahareh A. Mojarad, Worrawat Engchuan, Brett Trost, Ian Backstrom, Yue Yin, Bhooma Thiruvahindrapuram, Linda M. Pallotto, Aleksandra Mitina, Mahreen Khan, Giovanna Pellecchia, Bushra Haque, Keyi Guo, Tracy Heung, Gregory Costain, Stephen W. Scherer, Christian R. Marshall, Christopher E. Pearson, Anne S. Bassett, Ryan K. C. Yuen

Bibliographic record

VenueMolecular Psychiatry · 2022
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsToronto General HospitalSickKids FoundationUniversity Health NetworkUniversity of TorontoCentre for Addiction and Mental HealthHospital for Sick Children
FundersHospital for Sick ChildrenAzrieli FoundationCanadian Institute for Advanced ResearchChildren’s Hospital of Wisconsin Research InstituteCanadian Institutes of Health ResearchGenome CanadaGovernment of CanadaFondation Brain Canada
KeywordsSchizophrenia (object-oriented programming)Genome-wide association studyGenetic associationGeneticsPopulationTandem repeatBiologyGenomePsychiatryMedicineGeneSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Tandem repeat expansions (TREs) can cause neurological diseases but their impact in schizophrenia is unclear. Here we analyzed genome sequences of adults with schizophrenia and found that they have a higher burden of TREs that are near exons and rare in the general population, compared with non-psychiatric controls. These TREs are disproportionately found at loci known to be associated with schizophrenia from genome-wide association studies, in individuals with clinically-relevant genetic variants at other schizophrenia loci, and in families where multiple individuals have schizophrenia. We showed that rare TREs in schizophrenia may impact synaptic functions by disrupting the splicing process of their associated genes in a loss-of-function manner. Our findings support the involvement of genome-wide rare TREs in the polygenic nature of schizophrenia.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0040.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.242
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations43
Published2022
Admission routes2
Has abstractyes

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