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Record W2129095074 · doi:10.1002/ajmg.b.32137

Meta‐analysis of association between obsessive‐compulsive disorder and the 3′ region of neuronal glutamate transporter gene <i>SLC1A1</i>

2013· review· en· W2129095074 on OpenAlexafffund
S. Evelyn Stewart, C Mayerfeld, Paul Arnold, Jacquelyn Crane, Colm O’Dushlaine, Jesen Fagerness, Dongmei Yu, Jeremiah M. Scharf, Elaine Chan, F. Kassam, Pablo R. Moya, Jens R. Wendland, Richard Delorme, Margaret A. Richter, James L. Kennedy, Jeremy Veenstra‐VanderWeele, Jack Samuels, Benjamin D. Greenberg, James T. McCracken, James A. Knowles, Abby J. Fyer, Scott L. Rauch, Mark A. Riddle, Marco A. Grados, O. Joseph Bienvenu, Bernadette Cullen, Y. Wang, Yin Yao Shugart, John Piacentini, Steven A. Rasmussen, Gerald Nestadt, Dennis L. Murphy, Michael A. Jenike, Edwin H. Cook, David L. Pauls, Gregory L. Hanna, Carol A. Mathews

Bibliographic record

VenueAmerican Journal of Medical Genetics Part B Neuropsychiatric Genetics · 2013
Typereview
Languageen
FieldPsychology
TopicObsessive-Compulsive Spectrum Disorders
Canadian institutionsCentre for Addiction and Mental HealthSunnybrook Health Science CentreUniversity of British ColumbiaHospital for Sick ChildrenUniversity of TorontoBC Mental Health & Substance Use Services
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthCanadian Institutes of Health ResearchH. Lundbeck A/SNational Institutes of HealthEli Lilly CanadaAmerican Academy of Child and Adolescent PsychiatryInternational OCD FoundationEli Lilly and Company
KeywordsGenome-wide association studyCandidate geneSingle-nucleotide polymorphismGenetic associationGeneticsBiologySNPMeta-analysisGeneBioinformaticsMedicineGenotypeInternal medicine

Abstract

fetched live from OpenAlex

The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3' end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P = 0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N = 358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P = 0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD.

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)0.011
metaresearch head score (Gemma)0.018
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.011
Threshold uncertainty score0.056

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0110.018
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0080.030
Bibliometrics0.0030.005
Science and technology studies0.0010.001
Scholarly communication0.0030.001
Open science0.0020.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0030.000

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 head0.038
GPT teacher head0.324
Teacher spread0.286 · 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 designMeta-analysis
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

Citations104
Published2013
Admission routes2
Has abstractyes

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Same venueAmerican Journal of Medical Genetics Part B Neuropsychiatric GeneticsSame topicObsessive-Compulsive Spectrum DisordersFrench-language works237,207