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Early Manifestations of Neurodevelopmental Copy Number Variants in Children: A Population-Based Investigation

2025· article· en· W4408471213 on OpenAlexfundno aff
Charlotte Dennison, Joanna Martin, Amy Shakeshaft, Lucy Riglin, Victoria Powell, George Kirov, Michael John Owen, Michael O‘Donovan, Anita Thapar

Bibliographic record

VenueBiological Psychiatry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsnot available
FundersCalgary Arts DevelopmentWolfson FoundationUniversity of BristolCardiff UniversityNational Institute for Health and Care ResearchLlywodraeth CymruHealth and Care Research WalesWellcome TrustMedical Research CouncilWellcome
KeywordsCopy-number variationNeurodevelopmental disorderGeneticsMedicineBiologyGenomeGene

Abstract

fetched live from OpenAlex

BACKGROUND: There is clinical interest in recognizing copy number variants (CNVs) in children because many have immediate and long-term health implications. Neurodevelopmental (ND) CNVs are associated with intellectual disability, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD), conditions typically diagnosed by medical practitioners. However, ND CNVs may have additional, early developmental impacts that have yet to be examined in unselected populations. METHODS: Carriers of known ND CNVs were identified in 2 UK birth cohorts: ALSPAC (Avon Longitudinal Study of Parents and Children) (carriers = 144, controls = 6217) and MCS (Millennium Cohort Study) (carriers = 151, controls = 6559). In ALSPAC, we assessed associations between CNV carrier status and birth complications; preschool development; cognitive ability; ND conditions (ASD, ADHD, reading, language, and motor difficulties); and psychiatric, social, and educational outcomes. Corresponding phenotypes were identified in MCS and meta-analyzed, where available. RESULTS: In ALSPAC, ND CNVs were associated with low cognitive ability, ADHD, and ASD. ND CNV carriers showed a greater likelihood of preterm birth, fine and gross motor delay, difficulties in motor coordination, language, and reading, and special educational needs (SEND). Meta-analysis with available measures in MCS identified elevated likelihood of ASD, ADHD, low birth weight, reading difficulties, SEND, and peer problems. CONCLUSIONS: ND CNVs are associated with a broad range of developmental impacts. While clinicians who see children with intellectual disability, ASD, or ADHD may be aware of the impacts of CNVs and consider genetic testing, our investigation suggests that this training and awareness may need to extend to other professional groups (e.g., speech and language therapists).

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.350

Codex and Gemma teacher scores by category

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

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 head0.236
Teacher spread0.228 · 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.

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

Citations8
Published2025
Admission routes1
Has abstractyes

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