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Polygenic Multiple Sclerosis Risk and Population-Based Childhood Brain Imaging.

C Louk de Mol1,2, Philip R Jansen1,3,4,5,6, Ryan L Muetzel1,3

  • 1Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.

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|March 13, 2020
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Summary
This summary is machine-generated.

Genetic predisposition for multiple sclerosis (MS) is linked to increased white matter integrity in children. This suggests genetic risk factors for MS influence brain development early in life.

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Area of Science:

  • Neuroscience
  • Genetics
  • Pediatric Imaging

Background:

  • Multiple sclerosis (MS) is a neurological disorder with significant genetic influences and immune-mediated neurodegeneration.
  • MS patients exhibit distinct brain structures, including reduced regional volumes and altered white matter (WM) microstructure.
  • The relationship between genetic MS risk and brain structure during early development is not well understood.

Purpose of the Study:

  • To investigate the association between polygenic risk scores (PRS) for MS and brain imaging outcomes in a large, population-based pediatric cohort.
  • To gain insights into the neurobiological underpinnings of MS by examining early brain development.
  • To determine if genetic susceptibility for MS correlates with specific brain structural metrics in children.

Main Methods:

  • Utilized data from the Generation R Study, including genotyped participants aged 8–12 years.
  • Collected T1-weighted volumetric and diffusion tensor imaging (DTI) data from 1,136 and 1,088 participants, respectively.
  • Calculated MS PRS based on a large genome-wide association study and performed linear regression analyses with brain imaging outcomes (regional volumes, fractional anisotropy [FA], mean diffusivity).

Main Results:

  • No significant associations were found between MS PRS and regional brain volumes.
  • A positive association was observed between MS PRS and global white matter fractional anisotropy (FA) (p < 0.001).
  • Tract-specific analyses revealed higher FA and lower radial diffusivity in several white matter tracts, with findings replicated in an independent pediatric sample.

Conclusions:

  • This study provides the first evidence linking a higher genetic predisposition for MS with increased global white matter FA in early childhood within the general population.
  • The findings suggest a critical preadolescent developmental window where MS risk variants impact brain structure.
  • These results highlight the potential for early neurodevelopmental insights into the pathophysiology of multiple sclerosis.