# Assessment of Brain Morphological Abnormalities and Neurodevelopmental Risk Copy Number Variants in Individuals from the UK Biobank

## TL;DR

This study links genetic deletions to brain structure changes in neurodevelopmental and neuropsychiatric disorders using UK Biobank data.

## Contribution

The study identifies specific CNVs associated with brain morphological changes and their role in neuropsychiatric risk.

## Key findings

- Deletions in specific genomic areas correlate with brain region size differences like corpus callosum and cerebellum.
- Neuroanatomical changes linked to CNVs are associated with neuropsychiatric disorder risk.
- Gene sets in these regions are enriched for brain development pathways and NDD-related phenotypes.

## Abstract

Brain morphological abnormalities are common in patients with neurodevelopmental disorders (NDDs) and other neuropsychiatric disorders, often reflecting abnormal brain development and function. Genetic studies have found common genetic factors in NDDs and other neuropsychiatric disorders, although the etiology of brain structural changes in these disorders remains poorly understood. In this study, we analyzed magnetic resonance imaging (MRI) and genetic data from more than 30K individuals from the UK Biobank to evaluate whether NDD-risk copy number variants (CNVs) are also associated with neuroanatomical changes in both patients and neurotypical individuals. We found that the size differences in brain regions such as corpus callosum and cerebellum were associated with the deletions of specific areas of the human genome, and that specific neuroanatomical changes confer a risk of neuropsychiatric disorders. Furthermore, we observed that gene sets located in these genomic regions were enriched for pathways crucial for brain development and for phenotypes commonly observed in patients with NDDs. These findings highlight the link between CNVs, brain structure abnormalities, and the shared pathophysiology of NDDs and other neuropsychiatric disorders, providing new insights into the underlying mechanisms of these disorders and the identification of potential biomarkers for better diagnosis.