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Record W2800380700 · doi:10.1093/schbul/sby038

The Emerging Immunogenetic Architecture of Schizophrenia

2018· review· en· W2800380700 on OpenAlexafffund
Jennie G. Pouget

Bibliographic record

VenueSchizophrenia Bulletin · 2018
Typereview
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsCentre for Addiction and Mental Health
FundersCanadian Institutes of Health Research
KeywordsImmune systemGenome-wide association studySchizophrenia (object-oriented programming)DiseasePleiotropyGenetic architectureImmune dysregulationGenetic associationBiologyImmunologyNeuroscienceGeneMedicineGeneticsPhenotypeSingle-nucleotide polymorphismPsychiatry

Abstract

fetched live from OpenAlex

Schizophrenia is a severe psychiatric disorder of complex etiology. Immune processes have long been proposed to contribute to the development of schizophrenia, and accumulating evidence supports immune involvement in at least a subset of cases. In recent years, large-scale genetic studies have provided new insights into the role of the immune system in this disease. Here, we provide an overview of the immunogenetic architecture of schizophrenia based on findings from genome-wide association studies (GWAS). First, we review individual immune loci identified in secondary analyses of GWAS, which implicate over 30 genes expressed in both immune and brain cells. The function of the proteins encoded by these immune candidates highlight the role of the complement system, along with regulation of apoptosis in both immune and neuronal cells. Next, we review hypothesis-free pathway analyses which have so far been inconclusive with respect to identifying immune pathways involved in schizophrenia. Finally, we explore the genetic overlap between schizophrenia and immune-mediated diseases. Although there have been some inconsistencies across studies, genome-wide pleiotropy has been reported between schizophrenia and Crohn's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and ulcerative colitis. Overall, there are multiple lines of evidence supporting the role of immune genes in schizophrenia. Current evidence suggests that specific immune pathways are involved-likely those with dual functions in the central nervous system. Future studies focused on further elucidating the relevant pathways hold the potential to identify novel biomarkers and therapeutic targets for 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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.987
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0030.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.002

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 head0.028
GPT teacher head0.288
Teacher spread0.260 · 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 teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreReview

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

Citations80
Published2018
Admission routes2
Has abstractyes

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