Linkage analysis suggests a region of importance for multiple sclerosis in 3p14-13

Four genomic screens for linkage in multiple sclerosis (MS) have been reported. They confirmed the established role of the human leucocyte antigen (HLA) complex genes in MS and, in addition, suggested the importance of a few other chromosomal segments. Here we report evidence for the importance of 3p14-13 region identified by suggestive linkage in genomic screens from Canada and the United Kingdom. When studying 146 Nordic MS multiplex families, mostly affected sib-pairs, with eight microsatellite markers, spanning a 36-cM region, we observed a two-point non-parametric linkage (NPL) score of 2.39 (P = 0.007) by the GENEHUNTER package for marker D3S1285 and a multipoint NPL score of 1.20 in the same region. Association studies in Swedish MS patients revealed modest allelic associations of uncertain significance not supported by transmission analysis. Analysis of the trinucleotide repeat sequence of the SCA7 gene in Swedish index cases did not reveal expansions. We conclude that support was obtained for the location of a gene or genes with importance for MS susceptibility in 3p14-13 region.