Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage to chromosome 1q44

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disease with a strong genetic component. Numerous studies have failed to consistently identify genes that confer disease susceptibility except for association with HLA-DR. Seven non-HLA regions (1q, 2q, 9q, 13q, 16q, 18p and 19q) identified in a recent genomic screen were investigated by genotyping ∼20 single-nucleotide polymorphisms (SNPs) at ∼1 Mb intervals. Non-parametric multipoint analyses identified a peak LOD * score of 2.99 for the 1q44 region and substantially narrowed the linkage peak to ∼7 Mb. Ordered subset analyses (OSA) identified significant LOD score increases for 2q35 and 18p11 when ranking families by HLA-DR status and identified a significant LOD score increase in region 2q35 when ranking families by linkage to chromosome 1q44. 1q44 is particularly interesting because of linkage evidence for this region in studies of both rheumatoid arthritis and systemic lupus erythematosus.