Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.

A recent genome-wide association study by the International Multiple Sclerosis Genetics Consortium (IMSGC) reported association of 17 single-nucleotide polymorphisms (SNPs) in 14 loci with multiple sclerosis (MS). Only two loci, HLA-DRA and IL2RA, reached genome-wide significance (P<5E-08). I...

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Main Authors: Hoppenbrouwers, I, Aulchenko, Y, Janssens, A, Ramagopalan, S, Broer, L, Kayser, M, Ebers, G, Oostra, B, van Duijn, C, Hintzen, R
Format: Journal article
Language:English
Published: 2009
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author Hoppenbrouwers, I
Aulchenko, Y
Janssens, A
Ramagopalan, S
Broer, L
Kayser, M
Ebers, G
Oostra, B
van Duijn, C
Hintzen, R
author_facet Hoppenbrouwers, I
Aulchenko, Y
Janssens, A
Ramagopalan, S
Broer, L
Kayser, M
Ebers, G
Oostra, B
van Duijn, C
Hintzen, R
author_sort Hoppenbrouwers, I
collection OXFORD
description A recent genome-wide association study by the International Multiple Sclerosis Genetics Consortium (IMSGC) reported association of 17 single-nucleotide polymorphisms (SNPs) in 14 loci with multiple sclerosis (MS). Only two loci, HLA-DRA and IL2RA, reached genome-wide significance (P<5E-08). In our study, we determined whether we could replicate the results of the IMSGC and whether more SNPs are genome-wide significantly associated with MS. We assessed the association between the 17 IMSGC SNPs and MS in three cohorts (total number of subjects 3981, among these 1853 cases). We performed a meta-analysis of the results of our study, the original IMSGC results and the results of a recent replication study performed in the Australian population. Of the 17 IMSGC SNPs, five SNPs showed genome-wide significant association with MS: HLA-DRA (P=8E-124), IL7R (P=6E-09), IL2RA (P=1E-11), CD58 (P=4E-09) and CLEC16A (P=3E-12). Therefore, genome-wide significance has now been shown for SNPs in different non-HLA MS risk genes. Several of these risk genes, including CD58 and CLEC16A, are shared by different autoimmune diseases. Fine mapping studies will be needed to determine the functional contributions to distinct autoimmune phenotypes.
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spelling oxford-uuid:74287f02-f61e-41e8-86f3-2ec6f17e65092022-03-26T20:00:59ZReplication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:74287f02-f61e-41e8-86f3-2ec6f17e6509EnglishSymplectic Elements at Oxford2009Hoppenbrouwers, IAulchenko, YJanssens, ARamagopalan, SBroer, LKayser, MEbers, GOostra, Bvan Duijn, CHintzen, RA recent genome-wide association study by the International Multiple Sclerosis Genetics Consortium (IMSGC) reported association of 17 single-nucleotide polymorphisms (SNPs) in 14 loci with multiple sclerosis (MS). Only two loci, HLA-DRA and IL2RA, reached genome-wide significance (P<5E-08). In our study, we determined whether we could replicate the results of the IMSGC and whether more SNPs are genome-wide significantly associated with MS. We assessed the association between the 17 IMSGC SNPs and MS in three cohorts (total number of subjects 3981, among these 1853 cases). We performed a meta-analysis of the results of our study, the original IMSGC results and the results of a recent replication study performed in the Australian population. Of the 17 IMSGC SNPs, five SNPs showed genome-wide significant association with MS: HLA-DRA (P=8E-124), IL7R (P=6E-09), IL2RA (P=1E-11), CD58 (P=4E-09) and CLEC16A (P=3E-12). Therefore, genome-wide significance has now been shown for SNPs in different non-HLA MS risk genes. Several of these risk genes, including CD58 and CLEC16A, are shared by different autoimmune diseases. Fine mapping studies will be needed to determine the functional contributions to distinct autoimmune phenotypes.
spellingShingle Hoppenbrouwers, I
Aulchenko, Y
Janssens, A
Ramagopalan, S
Broer, L
Kayser, M
Ebers, G
Oostra, B
van Duijn, C
Hintzen, R
Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
title Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
title_full Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
title_fullStr Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
title_full_unstemmed Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
title_short Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.
title_sort replication of cd58 and clec16a as genome wide significant risk genes for multiple sclerosis
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