Burden of risk variants correlates with phenotype of multiple sclerosis

Mult Scler. 2015 Nov;21(13):1670-80. doi: 10.1177/1352458514568174. Epub 2015 May 6.


Background: More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown.

Objective: The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation.

Methods: A cumulative genetic risk score was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric analyses were applied.

Results: An increased genetic risk is observed for MS patients, including subsets such as oligoclonal band-negative and primary progressive MS patients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset.

Conclusion: MS patients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MS patients, the HLA region influences intrathecal IgG levels.

Keywords: IgG index; Multiple sclerosis; disease course; genetic association; genetic risk; oligoclonal bands; relapse rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Belgium / epidemiology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • HLA Antigens / genetics*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid*
  • Male
  • Multiple Sclerosis, Chronic Progressive / epidemiology*
  • Multiple Sclerosis, Chronic Progressive / genetics*
  • Oligoclonal Bands / cerebrospinal fluid
  • Oligoclonal Bands / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Recurrence
  • Risk Factors


  • HLA Antigens
  • Immunoglobulin G
  • Oligoclonal Bands