Linkage and association analysis of susceptibility regions on chromosomes 5 and 6 in 106 Scandinavian sibling pair families with multiple sclerosis

In the genetically homogeneous Scandinavian population, we have investigate d chromosome 5 and the HLA (human leukocyte antigen) region on chromosome 6 p21 by applying linkage and association analyses on 106 white sibling pair families with multiple sclerosis. The importance of genes within the HLA re gion for the susceptibility of multiple sclerosis has previously been repor ted. More recently, findings have suggested importance of regions on chromo some 5. Half of chromosome 5 was analyzed by using 14 microsatellite marker s and a susceptibility region with a maximum LOD score of 1.1 was identifie d Chromosome 6 was analyzed by HLA-DR typing and using the TNF alpha micros atellite marker. A peak, maximum LOD score of 2.0 was found at the HLA-DR m arker. Association studies were made for all the markers, comparing 106 pro bands hom the sibling pairs with 100 unrelated controls. None of the marker s on chromosome 5 showed significant association with multiple sclerosis, w hereas strong association between multiple sclerosis and DR2 was found, wit h an odds ratio of 3.7 (p < 10(-5)). It is surprising that association was not seen for any of the TNF alpha alleles including the 121-bp allele, alth ough this allele was in positive linkage disequilibrium with DR2 in both pa tients and controls. Our results support the existence of multiple sclerosi s susceptibility loci on chromosomes 5p and 6p21.