Genomic regions associated with multiple sclerosis are active in B cells.

More than 50 genomic regions have now been shown to influence the risk of multiple sclerosis (MS). However, the mechanisms of action, and the cell types in which these associated variants act at the molecular level remain largely unknown. This is especially true for associated regions containing no...

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Autores principales:	Giulio Disanto, Geir Kjetil Sandve, Antonio J Berlanga-Taylor, Julia M Morahan, Ruth Dobson, Gavin Giovannoni, Sreeram V Ramagopalan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/541fa2c204794509a8299aba3a99f8e9
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spelling	oai:doaj.org-article:541fa2c204794509a8299aba3a99f8e92021-11-18T07:26:15ZGenomic regions associated with multiple sclerosis are active in B cells.1932-620310.1371/journal.pone.0032281https://doaj.org/article/541fa2c204794509a8299aba3a99f8e92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22396755/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203More than 50 genomic regions have now been shown to influence the risk of multiple sclerosis (MS). However, the mechanisms of action, and the cell types in which these associated variants act at the molecular level remain largely unknown. This is especially true for associated regions containing no known genes. Given the evidence for a role for B cells in MS, we hypothesized that MS associated genomic regions co-localized with regions which are functionally active in B cells. We used publicly available data on 1) MS associated regions and single nucleotide polymorphisms (SNPs) and 2) chromatin profiling in B cells as well as three additional cell types thought to be unrelated to MS (hepatocytes, fibroblasts and keratinocytes). Genomic intervals and SNPs were tested for overlap using the Genomic Hyperbrowser. We found that MS associated regions are significantly enriched in strong enhancer, active promoter and strong transcribed regions (p = 0.00005) and that this overlap is significantly higher in B cells than control cells. In addition, MS associated SNPs also land in active promoter (p = 0.00005) and enhancer regions more than expected by chance (strong enhancer p = 0.0006; weak enhancer p = 0.00005). These results confirm the important role of the immune system and specifically B cells in MS and suggest that MS risk variants exert a gene regulatory role. Previous studies assessing MS risk variants in T cells may be missing important effects in B cells. Similar analyses in other immunological cell types relevant to MS and functional studies are necessary to fully elucidate how genes contribute to MS pathogenesis.Giulio DisantoGeir Kjetil SandveAntonio J Berlanga-TaylorJulia M MorahanRuth DobsonGavin GiovannoniSreeram V RamagopalanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32281 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giulio Disanto Geir Kjetil Sandve Antonio J Berlanga-Taylor Julia M Morahan Ruth Dobson Gavin Giovannoni Sreeram V Ramagopalan Genomic regions associated with multiple sclerosis are active in B cells.
description	More than 50 genomic regions have now been shown to influence the risk of multiple sclerosis (MS). However, the mechanisms of action, and the cell types in which these associated variants act at the molecular level remain largely unknown. This is especially true for associated regions containing no known genes. Given the evidence for a role for B cells in MS, we hypothesized that MS associated genomic regions co-localized with regions which are functionally active in B cells. We used publicly available data on 1) MS associated regions and single nucleotide polymorphisms (SNPs) and 2) chromatin profiling in B cells as well as three additional cell types thought to be unrelated to MS (hepatocytes, fibroblasts and keratinocytes). Genomic intervals and SNPs were tested for overlap using the Genomic Hyperbrowser. We found that MS associated regions are significantly enriched in strong enhancer, active promoter and strong transcribed regions (p = 0.00005) and that this overlap is significantly higher in B cells than control cells. In addition, MS associated SNPs also land in active promoter (p = 0.00005) and enhancer regions more than expected by chance (strong enhancer p = 0.0006; weak enhancer p = 0.00005). These results confirm the important role of the immune system and specifically B cells in MS and suggest that MS risk variants exert a gene regulatory role. Previous studies assessing MS risk variants in T cells may be missing important effects in B cells. Similar analyses in other immunological cell types relevant to MS and functional studies are necessary to fully elucidate how genes contribute to MS pathogenesis.
format	article
author	Giulio Disanto Geir Kjetil Sandve Antonio J Berlanga-Taylor Julia M Morahan Ruth Dobson Gavin Giovannoni Sreeram V Ramagopalan
author_facet	Giulio Disanto Geir Kjetil Sandve Antonio J Berlanga-Taylor Julia M Morahan Ruth Dobson Gavin Giovannoni Sreeram V Ramagopalan
author_sort	Giulio Disanto
title	Genomic regions associated with multiple sclerosis are active in B cells.
title_short	Genomic regions associated with multiple sclerosis are active in B cells.
title_full	Genomic regions associated with multiple sclerosis are active in B cells.
title_fullStr	Genomic regions associated with multiple sclerosis are active in B cells.
title_full_unstemmed	Genomic regions associated with multiple sclerosis are active in B cells.
title_sort	genomic regions associated with multiple sclerosis are active in b cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/541fa2c204794509a8299aba3a99f8e9
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Genomic regions associated with multiple sclerosis are active in B cells.

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