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Record W4410895846 · doi:10.1101/2025.05.28.25328353

Mapping Cerebellar Morphology in 15q11.2 CNV Carriers Using Normative Modeling

2025· preprint· en· W4410895846 on OpenAlexfundno aff
Milin Kim, Esten H. Leonardsen, Saige Rutherford, Geir Selbæk, Karin Persson, Nils Eiel Steen, Olav B. Smeland, Geneviève Richard, Dag Alnæs, Rune Bøen, Ida E. Sønderby, Dennis van der Meer, Ole A. Andreassen, Lars T. Westlye, Thomas Wolfers, Torgeir Moberget

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchNational Institutes of HealthHelse Sør-Øst RHFIXICOH. Lundbeck A/SServierGenentechNorges ForskningsrådUniversitetet i OsloEisaiNordForskDeutsche ForschungsgemeinschaftBundesministerium für Bildung und ForschungNorthern California Institute for Research and EducationStiftelsen Kristian Gerhard JebsenUniversity of Southern CaliforniaPfizerBioClinicaBiogenU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbEuropean CommissionMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationAlzheimer's Association
KeywordsNormativeMorphology (biology)Normative model of decision-makingComputer sciencePolitical scienceBiologyZoologyLaw

Abstract

fetched live from OpenAlex

Copy number variations (CNVs) at the 15q11.2 locus of the human genome have been associated with altered brain structure and increased risk for neurodevelopmental and neuropsychiatric disorders. The cerebellum is increasingly seen as a crucial brain region for neurodevelopmental conditions, yet the effects of 15q11.2 CNVs on cerebellar morphology remain largely unclear. Importantly, 15q11.2 CNVs shows reduced or incomplete penetrance (meaning that not all CNV carriers are affected) and variable expressivity (meaning that symptoms may differ between individuals with the same genetic alteration). Thus, there is a need to not only assess group differences, but also to quantify anatomical variability at the individual level. Here, we address these issues using normative models of brain anatomy trained on large datasets (n > 52k, age range: 3-85) to assess both group and individual-level deviations in cerebellar anatomy in carriers of 15q11.2 deletions (n = 120, mean [SD] age= 64.95 [7.58]) and duplications (n = 149, mean [SD] age=64.31 [7.21]), compared to non-carriers (n = 19,028, mean [SD] age=64.31 [7.58]). Group-level case-control analyses revealed significantly smaller total and regional cerebellar volumes in both deletion and duplication carriers, though with small effect sizes. Individual-level deviation analyses, capturing pronounced alterations in specific individuals, revealed a heterogeneous pattern among carriers. Overall, our findings suggest that CNVs at the 15q11.2 locus exert modest and highly individualized effects on cerebellar morphology.

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)0.003
metaresearch head score (Gemma)0.010
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 score0.023
Threshold uncertainty score0.046

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.010
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.025
GPT teacher head0.260
Teacher spread0.235 · 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

Citations1
Published2025
Admission routes1
Has abstractyes

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