Journal
EUROPEAN JOURNAL OF NEUROLOGY
Volume 28, Issue 11, Pages 3731-3741Publisher
WILEY
DOI: 10.1111/ene.15019
Keywords
Epstein-Barr virus infections; genetic association studies; multiple sclerosis; T lymphocytes; vitamin D
Categories
Funding
- Dutch MS Research Foundation
- Erasmus University Medical Center
- Netherlands Organization for Health Research and Development
- Netherlands Organization for Scientific Research
- Ministry of Health, Welfare, and Sport
- Erasmus University Rotterdam
Ask authors/readers for more resources
This study found that genetic risk variants for multiple sclerosis affect T cell composition in children from the general population, with specific risk variants negatively correlating with CD8(+) T cell frequencies and positively associating with CD4(+)/CD8(+) T cell ratios.
Background and purpose Patients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population. Methods We included genotyped participants from the population-based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS-PRSs on total T cell numbers (n = 1261), CD4(+) and CD8(+) lineages, and subsets therein (n= 675). In addition, T-cell-specific PRSs were constructed based on functional pathway data. Results The MS-PRS negatively correlated with CD8(+) T cell frequencies (p = 2.92 x 10(-3)), which resulted in a positive association with CD4(+)/CD8(+) T cell ratios (p = 8.27 x 10(-9)). These associations were mainly driven by two of 195 genome-wide significant MS risk variants: the main genetic risk variant for MS, HLA-DRB1*15:01 and an HLA-B risk variant. We observed no significant associations for the T-cell-specific PRSs. Conclusions Our results suggest that MS-associated genetic variants affect T cell composition during childhood in the general population.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available