Multiple sclerosis: a haplotype association study.
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 5cM 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.
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3050, Australia.
Simon J
SJ
Foote
Justin P
JP
Rubio
Melanie
M
Bahlo
Trevor J
TJ
Kilpatrick
Terence P
TP
Speed
Jim
J
Stankovich
Rachel
R
Burfoot
Helmut
H
Butzkueven
Laura
L
Johnson
Chris
C
Wilkinson
Bruce
B
Taylor
Michele
M
Sale
Ingrid A F
IA
van der Mei
Joanne L
JL
Dickinson
Patricia
P
Groom
D006239:Haplotypes; D006801:Humans; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D013648:Tasmania / Q000453:epidemiology