A new study published in Cyborg and Bionic Systems shows that there is a substantial shared genetic basis between schizophrenia and the microstructure of the brain’s white matter, helping to better understand the biological mechanisms underlying this complex mental disorder.

Schizophrenia is a genetically influenced condition affecting about 1% of the global population and is characterized by hallucinations, delusions, disorganized thinking, and cognitive impairments. Although its exact origins remain unclear, genetic factors play a key role in the development of the disorder, and more than 200 significant DNA regions have already been linked to schizophrenia risk in previous studies.

White matter in the brain enables communication between different regions of the nervous system and is critical for transmitting neural signals. Its microstructure is measured using neuroimaging techniques such as diffusion tensor imaging (DTI), which assess parameters like fractional anisotropy (FA), mean diffusivity (MD), and tensor eigenvalues (λ1–λ3). Previous research has reported abnormalities in these measures in people with schizophrenia, but the precise genetic relationship between these changes and the disease had remained unclear.

The researchers analyzed large-scale genetic data, including more than 53,000 schizophrenia cases and 77,000 controls, as well as data from over 33,000 participants in the UK Biobank with white matter microstructure measurements across 48 brain tracts. Using conditional and conjunctional false discovery rate methods (condFDR/conjFDR), they identified hundreds of genetic variants shared between schizophrenia and various white matter metrics.

In total, 435 shared DNA loci were identified across different DTI parameters, including 49 loci common to all measures, while more than 150 loci were unique to specific eigenvalue-based microstructural metrics.

Notably, some of these shared loci showed asymmetry between the left and right hemispheres of the brain, suggesting side-specific genetic influences. In particular, regions such as the posterior thalamic radiation and the tapetum were associated with a greater number of shared genetic signals on the left side than on the right.

Functional annotation of these shared genetic variants revealed their involvement in neurodevelopment, synaptic organization, and regulation of gene activity in open chromatin regions. This aligns with theoretical models proposing that structural features of white matter are linked to atypical neural connectivity in schizophrenia.

Overall, the study strengthens the view that genetic factors affecting white matter microstructure partially overlap with schizophrenia risk factors and may help guide future research into the neurobiological basis of the disorder and the development of potential therapeutic strategies.