Identity-by-descent mapping to detect rare variants conferring susceptibility to Multiple Sclerosis

Lin, Rui, Charlesworth, Jac, Stankovich, Jim, Perreau, Victoria M., Brown, Matthew A. and Taylor, Bruce V. (2013) Identity-by-descent mapping to detect rare variants conferring susceptibility to Multiple Sclerosis. Plos One, 8 3: e56379.1-e56379.8. doi:10.1371/journal.pone.0056379

Author Lin, Rui
Charlesworth, Jac
Stankovich, Jim
Perreau, Victoria M.
Brown, Matthew A.
Taylor, Bruce V.
Title Identity-by-descent mapping to detect rare variants conferring susceptibility to Multiple Sclerosis
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-03
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0056379
Open Access Status DOI
Volume 8
Issue 3
Start page e56379.1
End page e56379.8
Total pages 8
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
Genome-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 = 1.9×10-6). 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
Keyword Genome wide association
Zinc finger protein
Genetic Dissection
Complex Traits
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 28 Apr 2013, 00:19:18 EST by System User on behalf of UQ Diamantina Institute