Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.

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 t...

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Autores principales:	Rui Lin, Jac Charlesworth, Jim Stankovich, Victoria M Perreau, Matthew A Brown, ANZgene Consortium, Bruce V Taylor
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d25e2232bc334290992608243f48933a
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spelling	oai:doaj.org-article:d25e2232bc334290992608243f48933a2021-11-18T07:54:59ZIdentity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.1932-620310.1371/journal.pone.0056379https://doaj.org/article/d25e2232bc334290992608243f48933a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472070/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Genome-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.Rui LinJac CharlesworthJim StankovichVictoria M PerreauMatthew A BrownANZgene ConsortiumBruce V TaylorPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e56379 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rui Lin Jac Charlesworth Jim Stankovich Victoria M Perreau Matthew A Brown ANZgene Consortium Bruce V Taylor Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
description	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.
format	article
author	Rui Lin Jac Charlesworth Jim Stankovich Victoria M Perreau Matthew A Brown ANZgene Consortium Bruce V Taylor
author_facet	Rui Lin Jac Charlesworth Jim Stankovich Victoria M Perreau Matthew A Brown ANZgene Consortium Bruce V Taylor
author_sort	Rui Lin
title	Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
title_short	Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
title_full	Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
title_fullStr	Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
title_full_unstemmed	Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
title_sort	identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d25e2232bc334290992608243f48933a
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Identity-by-descent mapping to detect rare variants conferring susceptibility to multiple sclerosis.

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