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Background: Multiple sclerosis (MS) prevalence is unevenly distributed worldwide. Immigration to Norway from countries with a lower MS prevalence is increasing. The aim of this study was to investigate MS prevalence in different immigrant populations in Norway and evaluate the effect of migrating from low- to high-risk regions of MS., Method: First- and second-generation immigrants from the largest immigrant populations were identified from the 2012 Norwegian prevalence study. Prevalence of MS in different ethnic groups was compared using the standardized prevalence ratio (SPR)., Results: European and North-American immigrants had the highest prevalence of MS, whereas African and Asian immigrants had the lowest. The prevalence of first-generation Iranian immigrants was not significantly different from the total Norwegian population (SPR 0.70, 95% CI: 0.46-1.03). Second-generation immigrants from Pakistan (SPR 1.62, 95% CI: 0.88-2.76) had a strong increase in prevalence compared to the first generation (SPR 0.13, 95% CI: 0.05-0.28)., Conclusion: MS prevalence among immigrants in Norway in general reflects the uneven distribution worldwide. The sharp increase in prevalence in immigrants seen in one generation suggests strong environmental factors affecting the MS risk in Norway., (© The Author(s), 2014.)

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10(-16)). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10(-7)). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10(-37)). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10(-22)), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10(-6)). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)