The genetic relationships between brain structure and schizophrenia.
Eva-Maria Stauffer1, Richard A I Bethlehem2,3, Lena Dorfschmidt2
1Department of Psychiatry, University of Cambridge, Cambridge, UK. ems206@cam.ac.uk.
Nature Communications
|November 28, 2023
Summary
Researchers identified 61 genes linking schizophrenia risk to brain structure variations. Genetic links between schizophrenia and brain phenotypes were strongest in key brain network hubs, suggesting neurodevelopmental origins.
Area of Science:
- Neurogenetics
- Psychiatric Genetics
- Neuroimaging Genetics
Background:
- Genetic factors influence schizophrenia risk, potentially through effects on brain structure.
- Identifying specific genes associated with both schizophrenia and cortical phenotypes is crucial for understanding these links.
Purpose of the Study:
- To identify genes associated with both schizophrenia and cortical structural metrics.
- To investigate the genetic covariation between schizophrenia and brain phenotypes across the cortex.
- To explore the neurodevelopmental basis of genetic risks for schizophrenia.
Main Methods:
- Utilized genome-wide association studies (GWAS) for schizophrenia and magnetic resonance imaging (MRI) metrics (surface area, cortical thickness, neurite density index).
- Employed Hi-C-coupled MAGMA and whole-genome partial least squares analysis to identify pleiotropic genes and genetic covariation.
- Conducted Mendelian randomization analysis to assess causality and compared pleiotropic associations across different disorders.
Main Results:
- Identified 61 genes significantly associated with both schizophrenia and at least one MRI metric.
- Demonstrated significant genetic covariation between schizophrenia and cortical area/thickness across most regions.
- Found that genetic covariation was strongest in hubs of structural covariance networks and associated genes were enriched for neurodevelopmental processes.
- Mendelian randomization suggested a potential causal role for posterior cingulate cortical area variation in schizophrenia risk.
- Pleiotropic associations with MRI metrics were stronger for schizophrenia than for bipolar disorder, Alzheimer's disease, or height.
Conclusions:
- Specific genes link schizophrenia to variations in cortical structure, particularly in key brain network hubs.
- Neurodevelopmental processes are implicated in the genetic etiology of schizophrenia.
- Genetic influences on specific cortical regions, like the posterior cingulate cortex, may causally contribute to schizophrenia risk.
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