Mapping Cerebellar Morphology in 15q11.2 CNV Carriers Using Normative Modeling
Milin Kim1,2, Esten H Leonardsen1,2, Saige Rutherford3,4,5
1Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.
Medrxiv : the Preprint Server for Health Sciences
|July 15, 2025
Summary
Copy number variations (CNVs) in the 15q11.2 region impact cerebellar size modestly. These genetic changes cause varied effects on brain anatomy at the individual level, highlighting personalized impacts.
Area of Science:
- Neurogenetics
- Neuroimaging
- Human Genetics
Background:
- Copy number variations (CNVs) at the 15q11.2 locus are linked to neurodevelopmental and neuropsychiatric disorders.
- The cerebellum's role in neurodevelopment is increasingly recognized, but the impact of 15q11.2 CNVs on its structure is not well understood.
- 15q11.2 CNVs exhibit incomplete penetrance and variable expressivity, necessitating individual-level analysis.
Purpose of the Study:
- To investigate the effects of 15q11.2 deletions and duplications on cerebellar morphology.
- To assess both group-level and individual-level anatomical deviations in CNV carriers.
- To utilize normative models for precise quantification of cerebellar anatomy.
Main Methods:
- Employed normative models of brain anatomy trained on a large dataset (>52,000 individuals, ages 3-85).
- Analyzed cerebellar volumes in 15q11.2 deletion carriers (n=120) and duplication carriers (n=149) compared to non-carriers (n=19,028).
- Conducted both group-level case-control and individual-level deviation analyses.
Main Results:
- Group analyses showed significantly smaller total and regional cerebellar volumes in both deletion and duplication carriers, with small effect sizes.
- Individual-level analyses revealed heterogeneous patterns of cerebellar anatomical deviations among carriers.
- Findings indicate that 15q11.2 CNVs have modest effects on cerebellar morphology.
Conclusions:
- CNVs at the 15q11.2 locus are associated with subtle alterations in cerebellar morphology.
- The impact of 15q11.2 CNVs on cerebellar anatomy is highly individualized.
- Further research is needed to understand the clinical implications of these findings.
