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dc.contributor.authorLin, R
dc.contributor.authorCharlesworth, J
dc.contributor.authorStankovich, J
dc.contributor.authorPerreau, VM
dc.contributor.authorBrown, MA
dc.contributor.authorBaxter, A
dc.contributor.authorKermode, A
dc.contributor.authorBahlo, M
dc.contributor.authorCarroll, W
dc.contributor.authorButzkueven, H
dc.contributor.authorBooth, D
dc.contributor.authorStewart, G
dc.contributor.authorWiley, J
dc.contributor.authorField, J
dc.contributor.authorTajouri, L
dc.contributor.authorGriffiths, L
dc.contributor.authorBarnett, M
dc.contributor.authorMoscato, P
dc.contributor.authorHeard, R
dc.contributor.authorScott, R
dc.contributor.authorMcColl, S
dc.contributor.authorFoote, S
dc.contributor.authorBroadley, S
dc.contributor.authorSlee, M
dc.contributor.authorVucic, S
dc.contributor.authorKilpatrick, T
dc.contributor.authorTaylor, BV
dc.date.accessioned2017-05-03T14:21:09Z
dc.date.available2017-05-03T14:21:09Z
dc.date.issued2013
dc.date.modified2014-02-03T04:19:09Z
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0056379
dc.identifier.urihttp://hdl.handle.net/10072/56376
dc.description.abstractGenome-wide association studies (GWAS) have identified around 60 common variants associated with multiple sclerosis (MS), but these loci only explain a fraction of the heritability of MS. Some missing heritability may be caused by rare variants that have been suggested to play an important role in the aetiology of complex diseases such as MS. However current genetic and statistical methods for detecting rare variants are expensive and time consuming. 'Population-based linkage analysis' (PBLA) or so called identity-by-descent (IBD) mapping is a novel way to detect rare variants in extant GWAS datasets. We employed BEAGLE fastIBD to search for rare MS variants utilising IBD mapping in a large GWAS dataset of 3,543 cases and 5,898 controls. We identified a genome-wide significant linkage signal on chromosome 19 (LOD = 4.65; p = 1.9ױ0-6). Network analysis of cases and controls sharing haplotypes on chromosome 19 further strengthened the association as there are more large networks of cases sharing haplotypes than controls. This linkage region includes a cluster of zinc finger genes of unknown function. Analysis of genome wide transcriptome data suggests that genes in this zinc finger cluster may be involved in very early developmental regulation of the CNS. Our study also indicates that BEAGLE fastIBD allowed identification of rare variants in large unrelated population with moderate computational intensity. Even with the development of whole-genome sequencing, IBD mapping still may be a promising way to narrow down the region of interest for sequencing priority.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent1636445 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome56379-1
dc.relation.ispartofpagetoe56379-8
dc.relation.ispartofissue3
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume8
dc.rights.retentionY
dc.subject.fieldofresearchMedical and Health Sciences not elsewhere classified
dc.subject.fieldofresearchcode119999
dc.titleIdentity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2013 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.date.issued2013
gro.hasfulltextFull Text
gro.griffith.authorBroadley, Simon


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