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Identity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple Sclerosis

Citation

Lin, R and Charlesworth, J and Stankovich, J and Perreau, VM and Brown, MA and Taylor, BV, ANZgene Consortium, Identity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple Sclerosis, PLoS ONE, 8, (3) Article e56379. ISSN 1932-6203 (2013) [Refereed Article]


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Licensed under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/

DOI: doi:10.1371/journal.pone.0056379

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. © 2013 Lin et al.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Lin, R (Ms Lin)
Author:Charlesworth, J (Dr Jac Charlesworth)
Author:Stankovich, J (Dr Jim Stankovich)
Author:Taylor, BV (Professor Bruce Taylor)
ID Code:84531
Year Published:2013
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-05-16
Last Modified:2017-11-07
Downloads:259 View Download Statistics

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