Genetic and environmental mediators of multiple sclerosis susceptibility but not early severity run in families

Cato E A Corsten1, Ana M Marques2, Yifan van Hasselt2

  • 1Department of Neurology, MS Center ErasMS, Erasmus MC University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.

Abstract

Insights

Familial multiple sclerosis (MS) is linked to genetic susceptibility, low vitamin D, and high BMI, but does not affect the early disease course after clinically isolated syndrome (CIS). These factors influence MS risk, not progression.

Area of Science:

  • Neurology
  • Genetics
  • Immunology

Background:

  • Multiple sclerosis (MS) risk involves genetic and environmental factors.
  • Familial aggregation of MS is known, but its impact on early disease progression after clinically isolated syndrome (CIS) remains unclear.

Purpose of the Study:

  • To investigate the association of familial MS with genetic and environmental risk factors.
  • To examine the relationship between familial MS and the clinical presentation and disease course following CIS.

Main Methods:

  • A prospective cohort study of CIS participants within six months of symptom onset.
  • Assessment of family history, weighted genetic risk scores (wGRS) for MS, 25-hydroxyvitamin D (25(OH)D), body mass index (BMI), HLA-DRB1*15:01, and anti-Epstein Barr virus Nuclear Antigen-1 (anti-EBNA1) IgG.
  • Cox regression analysis to estimate associations with disease course.

Main Results:

  • Familial MS was reported by 19.5% of participants and associated with higher MS susceptibility wGRS and HLA-DRB1*15:01 carriership.
  • Participants with first-degree relatives with MS showed wGRS for lower 25(OH)D and higher adult BMI.
  • No significant differences in anti-EBNA1 IgG, 25(OH)D levels, baseline characteristics, or disease severity were observed between familial and non-familial MS groups.

Conclusions:

  • Familial MS is linked to increased genetic susceptibility, lower vitamin D, and higher BMI.
  • These factors are associated with MS risk but not with the early disease course after CIS.
  • MS susceptibility and disease course appear to be influenced by distinct pathophysiological pathways.

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