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Predicting brain structure in population-based samples with biologically informed genetic scores for schizophrenia
Sandra Van der Auwera1,2, Katharina Wittfeld2, Elena Shumskaya3,4
1Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Summary
Common genetic variants do not explain brain structure differences in healthy individuals at high genetic risk for schizophrenia. Additional factors like rare variants or environmental influences are likely involved in developing schizophrenia-related brain abnormalities.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia is linked to brain structural changes, including reduced gray and white matter volumes.
- The role of common genetic risk variants in causing these brain alterations in healthy individuals remains unclear.
- Previous studies investigating polygenic risk for schizophrenia and brain structure have yielded negative or unreplicated results.
Purpose of the Study:
- To investigate the association between biologically informed genetic risk scores for schizophrenia and brain structural phenotypes in healthy subjects.
- To determine if accumulated effects of specific schizophrenia risk variants (synaptic function, neurodevelopment, calcium signaling, glutamatergic neurotransmission) correlate with brain volumes.
- To explore a potential link between genetic predisposition to schizophrenia and observable brain structure differences.
Main Methods:
- Utilized whole-brain voxel-based morphometry (VBM) analyses in two population-based samples.
- Conducted regions of interest (ROIs) analyses in an independent replication sample.
- Calculated genetic risk scores based on selected schizophrenia risk variants across specific biological systems.
Main Results:
- No consistent associations were found between the biologically informed genetic risk scores and brain volumes in the studied samples.
- The genetic risk scores did not significantly predict structural brain abnormalities in healthy individuals.
- The findings did not support a direct link between common genetic variants for schizophrenia and brain structural phenotypes.
Conclusions:
- Common genetic variants alone do not appear to be sufficient to cause the structural brain abnormalities associated with schizophrenia in healthy individuals.
- Other factors, such as rare genetic variants, gene-gene interactions, or environmental influences (e.g., infection, trauma), may be necessary to trigger these brain changes.
- Further research is recommended to investigate gene-gene and gene-environment interactions in the context of schizophrenia and brain structure.
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