Oligoclonal bands and age at onset correlate with genetic risk score in multiple sclerosis. (May 2014)

• Record Type: Journal Article
• Authors: Harbo, Hanne F; Isobe, Noriko; Berg-Hansen, Pål; Bos, Steffan D; Caillier, Stacy J; Gustavsen, Marte W; Mero, Inger-Lise; Celius, Elisabeth Gulowsen; Hauser, Stephen L; Oksenberg, Jorge R; Gourraud, Pierre-Antoine
• Is Part Of: Multiple sclerosis. Volume 20:Number 6(2014)
• Page Start: 660
• Page End: 668
• Publication Date: 2014-05
• Subjects: Age of onset -- cerebrospinal fluid -- genetic association -- genetic risk -- genotype -- multiple sclerosis -- oligoclonal bands -- Multiple Sclerosis Genetic Burden; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458513506503
• Languages: English
• ISSNs: 1352-4585

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.