Mapping candidate non-MHC susceptibility regions to multiple sclerosis.
Understanding the genetic basis of multiple sclerosis (MS) remains a major challenge, despite decades of intensive research. In order to identify candidate non-MHC susceptibility regions to MS, the results of whole genome screens for linkage or association and follow-up studies in 18 different populations were superimposed together in a combined genomic map. Analysis of this map led to the prediction of at least 38 potential susceptibility regions, each showing linkage and/or association in several populations. Among these, 17 regions were the most reproducibly reported in these studies, thus representing top predicted candidates for MS. This non-formal approach to meta-analysis demonstrated the ability to verify results and retrieve lost information in an association study. Assessment of the map in a Northern Irish refined screen (n=415 cases, n=490 controls) revealed association in 15 regions (P<0.05), including 10 promising candidates on chromosomes 1p13, 2p13, 2q14, 3p23, 7q21, 13q14, 15q13, 17p13, 18q21 and 20p12 (P<0.0025). Seven of these regions were previously overlooked in the Northern Irish whole genome association study. Collating results from numerous studies, this draft map represents a tool that should facilitate the analysis of the genetic backgrounds of MS in many populations.
Abdeen
H
H
Regional Genetics Centre, Belfast City Hospital, Belfast, UK.
Heggarty
S
S
Hawkins
S A
SA
Hutchinson
M
M
McDonnell
G V
GV
Graham
C A
CA
D000328:Adult; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009103:Multiple Sclerosis / Q000235:genetics*; D016133:Polymerase Chain Reaction