Oligoclonal bands and age at onset correlate with genetic risk score in multiple sclerosis

Mult Scler. 2014 May;20(6):660-8. doi: 10.1177/1352458513506503. Epub 2013 Oct 7.


Background: Many genetic risk variants are now well established in multiple sclerosis (MS), but the impact on clinical phenotypes is unclear.

Objective: To investigate the impact of established MS genetic risk variants on MS phenotypes, in well-characterized MS cohorts.

Methods: Norwegian MS patients (n = 639) and healthy controls (n = 530) were successfully genotyped for 61 established MS-associated single nucleotide polymorphisms (SNPs). Data including and excluding Major Histocompatibility Complex (MHC) markers were summed to a MS Genetic Burden (MSGB) score. Study replication was performed in a cohort of white American MS patients (n = 1997) and controls (n = 708).

Results: The total human leukocyte antigen (HLA) and the non-HLA MSGB scores were significantly higher in MS patients than in controls, in both cohorts (P << 10(-22)). MS patients, with and without cerebrospinal fluid (CSF) oligoclonal bands (OCBs), had a higher MSGB score than the controls; the OCB-positive patients had a slightly higher MSGB than the OCB-negative patients. An early age at symptom onset (AAO) also correlated with a higher MSGB score, in both cohorts.

Conclusion: The MSGB score was associated with specific clinical MS characteristics, such as OCBs and AAO. This study underlines the need for well-characterized, large cohorts of MS patients, and the usefulness of summarizing multiple genetic risk factors of modest effect size in genotype-phenotype analyses.

Keywords: Age of onset; Multiple Sclerosis Genetic Burden; cerebrospinal fluid; genetic association; genetic risk; genotype; multiple sclerosis; oligoclonal bands.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Biomarkers / cerebrospinal fluid
  • Female
  • Genetic Testing
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Immunoglobulin G / cerebrospinal fluid
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / epidemiology*
  • Multiple Sclerosis / genetics*
  • Oligoclonal Bands / cerebrospinal fluid*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors


  • Biomarkers
  • Immunoglobulin G
  • Oligoclonal Bands