Brain functional connectivity mirrors genetic pleiotropy in psychiatric conditions
Clara A Moreau1,2,3, Kuldeep Kumar2, Annabelle Harvey2,3
1Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université Paris Cité, Paris, France.
Brain : a Journal of Neurology
|September 4, 2022
Summary
Genetic pleiotropy, where one gene affects multiple traits, links psychiatric disorders and cognitive functions. This study found shared brain functional network patterns, suggesting a genetic basis for these overlaps and potential for broad interventions.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Pleiotropy, a single genetic variant influencing multiple traits, is fundamental to psychiatric disorders.
- Genetic overlaps suggest potential overlaps in large-scale brain functional networks.
Purpose of the Study:
- To investigate if microscale genetic pleiotropy translates to macroscale brain functional network overlaps.
- To analyze the relationship between genetic risk, brain connectivity, and psychiatric conditions.
Main Methods:
- Utilized nine resting-state functional MRI datasets (32,726 individuals).
- Computed connectome-wide profiles for copy-number variants, polygenic scores, neuroticism, fluid intelligence, and psychiatric conditions.
- Correlated functional connectivity profiles with genetic and transcriptomic data.
Main Results:
- Nine of 19 condition/trait pairs showed significant functional connectivity correlations.
- Functional connectivity correlations showed high concordance with genetic (r=0.71) and transcriptomic (r=0.83) correlations.
- 30 out of 136 genetic risk connectivity profiles correlated above chance, driven by thalamus and somatomotor network overconnectivity.
Conclusions:
- A significant genetic component underlies shared brain connectivity profiles across psychiatric conditions and traits.
- Findings support pleiotropy's role in linking genes to behavior via brain networks.
- Identifies potential generalizable mechanisms for intervention across psychiatric disorders.
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