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Record W1992176272 · doi:10.1016/j.celrep.2014.10.015

A Role for Noncoding Variation in Schizophrenia

2014· article· en· W1992176272 on OpenAlexaff
Panos Roussos, Amanda Mitchell, Georgios Voloudakis, John F. Fullard, Venu Pothula, Jonathan Tsang, Eli A. Stahl, Anastasios Georgakopoulos, Douglas M. Ruderfer, Alexander W. Charney, Yukinori Okada, Katherine A. Siminovitch, Jane Worthington, Leonid Padyukov, Lars Klareskog, Peter K. Gregersen, Robert M. Plenge, Soumya Raychaudhuri, Menachem Fromer, Shaun Purcell, Kristen Brennand, Nikolaos K. Robakis, Eric E. Schadt, Schahram Akbarian, Pamela Sklar

Bibliographic record

VenueCell Reports · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsToronto General HospitalLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthNational Institute on AgingU.S. Department of Veterans AffairsNational Institute for Health and Care ResearchFriedman Brain Institute, Icahn School of Medicine at Mount SinaiWellcome TrustIcahn School of Medicine at Mount Sinai
KeywordsExpression quantitative trait lociBiologyGeneticsQuantitative trait locusLocus (genetics)Genome-wide association studyEnhancerRegulatory sequenceSingle-nucleotide polymorphismGeneSchizophrenia (object-oriented programming)Computational biologyRegulation of gene expressionGene expressionMedicine

Abstract

fetched live from OpenAlex

A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal cortex and -induced pluripotent stem cell-derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated noncoding SNPs and 3D genome architecture associated with chromosomal loopings and transcriptional regulation in the brain.

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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.008
GPT teacher head0.239
Teacher spread0.231 · 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

Citations271
Published2014
Admission routes1
Has abstractyes

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