Abstract
BACKGROUND: MS patients show abnormalities in white matter (WM) on brain imaging, with heterogeneity in the location of WM lesions. The "pothole" method can be applied to diffusion-weighted images to identify spatially distinct clusters of divergent brain WM microstructure.
OBJECTIVE: To investigate the association between genetic risk for MS and spatially independent clusters of decreased or increased fractional anisotropy (FA) in the brain. In addition, we studied sex- and age-related differences.
METHODS: 3 Tesla diffusion tensor imaging (DTI) data were collected in 8- to 12-year-old children from a population-based study. Global and tract-based potholes (lower FA clusters) and molehills (higher FA clusters) were quantified in 3047 participants with usable DTI data. A polygenic risk score (PRS) for MS was calculated in genotyped individuals (n = 1087) and linear regression analyses assessed the relationship between the PRS and the number of potholes and molehills, correcting for multiple testing using the False Discovery Rate.
RESULTS: The number of molehills increased with age, potholes decreased with age, and fewer potholes were observed in girls during typical development. The MS-PRS was positively associated with the number of molehills (β = 0.9, SE = 0.29, p = 0.002). Molehills were found more often in the corpus callosum (β = 0.3, SE = 0.09, p = 0.0003).
CONCLUSION: Genetic risk for MS is associated with spatially distinct clusters of increased FA during childhood brain development.
| Original language | English |
|---|---|
| Pages (from-to) | 13524585211034826 |
| Journal | Multiple Sclerosis |
| Volume | 28 |
| Issue number | 5 |
| Early online date | 11 Aug 2021 |
| DOIs | |
| Publication status | Published - Apr 2022 |
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financially supported by the Dutch Multiple Sclerosis Research Foundation. Neuroimaging in the Generation R study was supported by the Netherlands Organization for Health Research and Development (ZonMw) TOP project 91211021. The general design of the Generation R Study was made possible by financial support from the Erasmus Medical Center, the Erasmus University Rotterdam, the ZonMw, the NOW, and the Ministry of Health, Welfare, and Sport.
| Funders | Funder number |
|---|---|
| Now | |
| Netherlands Organization for Health Research and Development | |
| ZonMw | 91211021 |
| Erasmus Universiteit Rotterdam | |
| Ministerie van Volksgezondheid, Welzijn en Sport | |
| Stichting MS Research | |
| Erasmus Medisch Centrum |