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

Hanne F. Harbo, Noriko Isobe, Pål Berg-Hansen, Steffan D. Bos, Stacy J. Caillier, Marte W. Gustavsen, Inger Lise Mero, Elisabeth Gulowsen Celius, Stephen L. Hauser, Jorge R. Oksenberg, Pierre Antoine Gourraud

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)660-668
Number of pages9
JournalMultiple Sclerosis Journal
Volume20
Issue number6
DOIs
Publication statusPublished - May 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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