Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults
J Petrovska1, D Coynel2, V Freytag1
1Division of Molecular Neuroscience, Department of Biomedicine, University of Basel, CH-4055 Basel, Switzerland; Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, CH-4055 Basel, Switzerland.
Journal of the Neurological Sciences
|July 26, 2024
Summary
Genetic risk for multiple sclerosis (MS) is linked to lower working memory (WM) performance in healthy adults. MS polygenic risk scores (PRS) associated with WM, but not white matter integrity, suggesting distinct genetic pathways for MS risk and severity.
Area of Science:
- Neurogenetics
- Cognitive Neuroscience
- Neuroimmunology
Background:
- Multiple sclerosis (MS) is a complex neurological disorder with significant genetic heritability.
- MS is associated with cognitive impairments, particularly in working memory (WM).
- Brain abnormalities, including white matter changes, are characteristic of MS.
Purpose of the Study:
- To investigate the association between polygenic risk for MS and WM performance in healthy young adults.
- To examine the relationship between MS polygenic risk and white matter integrity (fractional anisotropy, FA).
- To explore genetic associations with MS severity in relation to WM and FA.
Main Methods:
- A polygenic risk score (PRS) for MS susceptibility was generated in 3282 healthy adults.
- The association between MS-PRS and WM performance was analyzed.
- The relationship between MS-PRS and white matter fractional anisotropy (FA) was assessed in a subsample.
Main Results:
- MS-PRS was significantly associated with lower WM performance in the lowest-performing individuals.
- No significant association was found between MS-PRS and white matter FA.
- MS severity PRS showed significant associations with mean FA, suggesting distinct genetic influences.
Conclusions:
- This study identifies a genetic link between MS susceptibility and WM performance in healthy individuals.
- The findings contribute to understanding the genetic complexity of MS and potential molecular pathways for cognitive deficits.
- Genetic associations with MS severity appear to involve different biological pathways than those related to overall MS risk.
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