Multiple sclerosis: A haplotype association study

Simon J. Foote, Justin P. Rubio, Melanie Bahlo, Trevor J. Kilpatrick, Terence P. Speed, Jim Stankovich, Rachel Burfoot, Helmut Butzkueven, Laura Johnson, Chris Wilkinson, Bruce Taylor, Michele Sale, Ingrid A.F. Van Der Mei, Joanne L. Dickinson, Patricia Groom

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Results are presented from a genomewide haplotype association study on multiple sclerosis (MS) cases from Tasmania, an island state of Australia. Cases were ascertained on strict clinical and radiological grounds and on the fact that they had at least one grandparent born in the state. This enriched for early settler chromosomes among present day Tasmanians with MS and increased the chances of finding common haplotype sharing at disease predisposition loci in distant relatives sharing common ancestral haplotypes. Four-to-five close relatives were also collected for each of 170 cases and 105 population-based controls. All were genotyped at a 5 cM resolution, haplotypes reconstructed and sharing estimated using an empirical approach based on sorting haplotypes to find the most common at each locus and then generating a test statistic for excess sharing in the cases based on permutation testing. Five initial loci were found where there was an excess sharing in the cases. These were fine-mapped with 10-12 additional markers. Only loci on chromosomes 6 and 10 remained after fine mapping. These loci demonstrate an increase in sharing of multi-marker haplotypes in MS cases compared to both population control transmitted haplotypes and case non-transmitted haplotypes.

Original languageEnglish
Title of host publicationGenetics of Autoimmunity
Number of pages9
Publication statusPublished - 1 Dec 2005

Publication series

NameNovartis Foundation Symposium
ISSN (Print)1528-2511

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