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White matter microstructural differences in children and genetic risk for multiple sclerosis: A population-based

C Louk de Mol1, Rinze F Neuteboom2, Philip R Jansen3

  • 1Department of Neurology, MS Center ErasMS, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands/The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|August 11, 2021
PubMed
Summary

Genetic risk for multiple sclerosis (MS) is linked to distinct white matter microstructural changes in children. This study reveals how genetic predisposition relates to brain development patterns in youth.

Keywords:
Multiple sclerosischild developmentepidemiologygenetic association studieswhite matter

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Area of Science:

  • Neuroimaging
  • Pediatric Neurology
  • Genetics

Background:

  • Multiple sclerosis (MS) patients exhibit white matter (WM) abnormalities on brain imaging, with varied lesion locations.
  • The "pothole" method analyzes diffusion-weighted images to identify distinct clusters of altered WM microstructure.

Purpose of the Study:

  • To examine the association between genetic risk for MS and independent clusters of decreased or increased fractional anisotropy (FA) in the brain.
  • To investigate sex- and age-related differences in these patterns.

Main Methods:

  • Diffusion tensor imaging (DTI) data were collected from 3047 children aged 8-12.
  • Quantified "potholes" (low FA clusters) and "molehills" (high FA clusters) globally and by tract.
  • Assessed the relationship between a polygenic risk score (PRS) for MS and the number of potholes/molehills using linear regression, correcting for multiple testing.

Main Results:

  • The number of molehills increased with age, while potholes decreased with age.
  • Fewer potholes were observed in girls during typical development.
  • A positive association was found between the MS polygenic risk score (PRS) and the number of molehills (β = 0.9, p = 0.002). Molehills were more prevalent in the corpus callosum.

Conclusions:

  • Genetic risk for MS is associated with distinct clusters of increased FA in the developing brain during childhood.