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

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 ...