Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence
Jakub Kopal1,2, Kuldeep Kumar3, Karin Saltoun1,2
1Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Nature Human Behaviour
|March 2, 2023
Summary
Copy number variations (CNVs) are genomic alterations impacting brain and behavior. Distinct CNVs converge on shared pathways, influencing multiple body systems and increasing risk for brain disorders.
Area of Science:
- Genetics and Neuroscience
- Developmental and Psychiatric Disorders
Background:
- Copy number variations (CNVs) are genomic deletions/duplications affecting brain and behavior.
- Previous studies suggest CNVs converge on shared mechanisms but examined single loci in small cohorts.
- Understanding how distinct CNVs contribute to similar disorders is crucial.
Purpose of the Study:
- To quantitatively dissect associations between brain organization and behavioral differentiation across 8 key CNVs.
- To explore CNV-specific brain morphology patterns and phenotypic profiles.
- To investigate the convergence of distinct CNVs on shared pathways and body-wide implications.
Main Methods:
- Analysis of brain morphology in 534 CNV carriers.
- Exploration of CNV-specific brain organization patterns.
- Annotation of CNV-associated patterns with ~1,000 lifestyle indicators from the UK Biobank.
Main Results:
- CNVs showed disparate morphological brain changes across multiple large-scale networks.
- Phenotypic profiles largely overlapped, with body-wide implications across cardiovascular, endocrine, skeletal, and nervous systems.
- Established population-level brain structural divergences and phenotypical convergences of CNVs.
Conclusions:
- Distinct CNVs can lead to similar phenotypic outcomes through shared neural and biological pathways.
- CNVs have broad, body-wide implications beyond the nervous system.
- This research provides insights into the etiology of major brain disorders.
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