Penetrance of Neurodevelopmental Copy Number Variants Is Associated With Variations in Cortical Morphology
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.084
- Threshold uncertainty score
- 0.495
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.254 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
BACKGROUND: Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance. METHODS: We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals (aged 7-90 years, 54% female), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 noncarriers. CNV penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk of developing either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder, and congenital malformations). RESULTS: For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus. CONCLUSIONS: Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.
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.
The record
- Venue
- Biological Psychiatry Cognitive Neuroscience and Neuroimaging
- Topic
- Genomic variations and chromosomal abnormalities
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Université de MontréalSickKids FoundationUniversity Health NetworkUniversity of TorontoCentre Hospitalier Universitaire Sainte-JustineInstitute for Clinical Evaluative SciencesCentre for Addiction and Mental Health
- Funders
- CilagFP7 HealthH2020 European Research CouncilNational Institute of Child Health and Human DevelopmentNational Institute of Biomedical Imaging and BioengineeringNational Institute of Mental HealthNorwegian Institute of Public HealthFaculty of Medicine and Health, University of SydneyNational Human Genome Research InstituteHelmholtz Zentrum MünchenHelse Sør-Øst RHFNational Health and Medical Research CouncilQatar Biomedical Research Institute, Hamad Bin Khalifa UniversityPerelman School of Medicine, University of PennsylvaniaNational Institutes of HealthMedical Research CouncilSickkids Research InstituteNew South Wales GovernmentAvera Institute for Human GeneticsCharles R. Drew University of Medicine and ScienceInstitut de Valorisation des DonnéesInstituto de Investigación Marqués de ValdecillaNorwegian Biodiversity Information CentreFreie Universität BerlinBundesministerium für Bildung und ForschungCanada First Research Excellence FundKhalifa University of Science, Technology and ResearchUniversity of Cape TownCommissariat à l'Énergie Atomique et aux Énergies AlternativesBergens ForskningsstiftelseUniversité de BordeauxH. Lundbeck A/SEuropean Federation of Pharmaceutical Industries and AssociationsInstitut National de la Santé et de la Recherche MédicaleHumboldt-Universität zu BerlinUniversitair Medisch Centrum GroningenPublic Health WalesUniversitätsmedizin GöttingenUniversitetet i BergenAstellas PharmaHelse Midt-NorgeVetenskapsrådetHamad Bin Khalifa UniversityHelse VestCentre National de la Recherche ScientifiqueDepartment of Health and Aged Care, Australian GovernmentFudan UniversitySchool of Psychology, Cardiff UniversityInnovative Medicines InitiativeSiemens HealthineersFondation pour la Recherche MédicaleSociété d'Accélération du Transfert de TechnologiesVrije Universiteit AmsterdamZonMwInstitute of Psychiatry, Psychology and Neuroscience, King’s College LondonKoninklijke Nederlandse Akademie van WetenschappenNational Natural Science Foundation of ChinaKarolinska InstitutetNational Institute for Health and Care ResearchUniversity of QueenslandSorbonne UniversitéQueensland University of TechnologyNorges ForskningsrådStockholms Läns LandstingUniversity of New South WalesSouth African Medical Research CouncilRijksuniversiteit GroningenNational Science FoundationNateraUniversity of TorontoKing's College LondonImperial College LondonUniversidad de SevillaRoyal College of Surgeons in IrelandPsychiatry Research TrustUniversität GreifswaldDeutsche ForschungsgemeinschaftAssistance publique-Hôpitaux de ParisBiogenWellcome TrustAgence Nationale de la RechercheQIMR Berghofer Medical Research InstituteMinistry of Cultural AffairsAustralian GovernmentHaukeland UniversitetssjukehusChildren's Hospital of PhiladelphiaSimons Foundation Autism Research InitiativeFédération pour la Recherche sur le CerveauUniversity of OxfordNeuroscience Research AustraliaCanadian Institutes of Health ResearchEuropean CommissionUniversity of UtahFondation Brain CanadaNorges Teknisk-Naturvitenskapelige UniversitetGeorgia State UniversityFoundation for the National Institutes of HealthUniversity of Southern CaliforniaInstituto de Salud Carlos IIIUniversidad de CantabriaUniversitetet i OsloFondation de l'Avenir pour la Recherche Médicale AppliquéeInstituto de Física de CantabriaAutism SpeaksEmory UniversityTechnische Universität DresdenFondation de FranceUniversity of PennsylvaniaQueensland Brain InstituteUniversité Paris-SaclayHospital for Sick ChildrenSunovionStanford Maternal and Child Health Research InstituteUniversity of RoehamptonNederlandse Organisatie voor Wetenschappelijk OnderzoekMcGill UniversityCentre for Medical Systems BiologyQatar FoundationServierUniversity of GalwayCardiff UniversityCompute CanadaScience Foundation Ireland
- Keywords
- PenetranceCopy-number variationMorphology (biology)BiologyEvolutionary biologyGeneticsPhenotypeGeneGenome
- Has abstract in OpenAlex
- yes