# The Genetic Architecture of the Human Corpus Callosum and its Subregions

## TL;DR

This study identifies genetic factors influencing the structure of the human corpus callosum and links them to prenatal development and neuropsychiatric disorders.

## Contribution

The study uses AI to analyze CC morphology and reveals novel genetic associations with prenatal growth and immune-driven thinning.

## Key findings

- Genetic variants linked to CC morphology are associated with prenatal intracellular organization and cell growth.
- Immune-mediated programmed cell death is implicated in thinning of the posterior body and isthmus of the CC.
- Genetic overlap is found between CC features and neuropsychiatric disorders like ADHD, bipolar disorder, and Parkinson’s disease.

## Abstract

The corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses and performing associative or executive functions. Identifying which genetic variants underpin CC morphometry can provide molecular insights into the CC’s role in mediating cognitive processes. We developed and used an artificial intelligence based tool to extract the midsagittal CC’s total and regional area and thickness in two large public datasets. We performed a genome-wide association study (GWAS) meta-analysis of European participants (combined N = 46,685) with generalization to the non-European participants (combined N = 7040). Post-GWAS analyses implicated prenatal intracellular organization and cell growth patterns, and high heritability in regions of open chromatin. Results suggest programmed cell death mediated by the immune system drives the thinning of the posterior body and isthmus. Genetic overlap, and causal genetic liability, between the CC, cerebral cortex features, and neuropsychiatric disorders such as attention-deficit/hyperactivity, bipolar disorders, and Parkinson’s disease were identified.

The corpus callosum is essential for coordinating sensorimotor, associative and executive functions. Here, the authors show a GWAS of corpus callosum morphology implicates prenatal growth pathways, immune-driven thinning, and genetic overlap with cortical and neuropsychiatric traits.