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Mapping Focal and Generalized Effects of Common Genetic Variants on Human Brain Structure
Biorxiv : the Preprint Server for Biology
|July 29, 2026
Summary
Genome-wide association studies reveal localized genetic influences on brain structure, with some variants affecting widespread brain differences. This research maps genetic effects on gray matter volume across the entire brain.
Area of Science:
- Neurogenetics
- Neuroimaging
- Human Brain Anatomy
Background:
- Genome-wide association studies (GWAS) identify genetic variants influencing brain structure and function.
- Hundreds of common variants linked to subcortical brain volumes raise questions about shared genetic architecture across brain networks.
Purpose of the Study:
- To create brain-wide maps of genetic influences on gray matter volume.
- To investigate localized versus distributed genetic effects on brain structure using polygenic scores (PGS).
Main Methods:
- Computed polygenic scores (PGS) from GWAS loci associated with ten brain regions of interest (ROIs).
- Utilized voxel-based morphometry (VBM) on 3D MRI scans to map gray matter volume (GMV) associations with PGS.
- Analyzed an independent sample from the discovery GWAS for validation.
Main Results:
- Found statistically significant, localized effects for PGS associated with the amygdala, thalamus, and basal ganglia.
- Discovered that PGS for brainstem volume showed widespread associations across the entire brain.
- Generated novel brain-wide maps illustrating genetic influences on brain structure.
Conclusions:
- Genetic influences on brain structure can be both localized and distributed.
- Brain-wide mapping provides a new method for interpreting the genomic architecture of brain structure.
- Findings offer insights into the genetic underpinnings of human brain anatomy.
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