Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.

Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (...

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Main Authors: Ana M Valdes, Unnur Styrkarsdottir, Michael Doherty, David L Morris, Massimo Mangino, Agu Tamm, Sally A Doherty, Kalle Kisand, Irina Kerna, Ann Tamm, Margaret Wheeler, Rose A Maciewicz, Weiya Zhang, Kenneth R Muir, Elaine M Dennison, Deborah J Hart, Sarah Metrustry, Ingileif Jonsdottir, Gudbjorn F Jonsson, Helgi Jonsson, Thorvaldur Ingvarsson, Cyrus Cooper, Timothy J Vyse, Tim D Spector, Kari Stefansson, Nigel K Arden
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023371&type=printable
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author Ana M Valdes
Unnur Styrkarsdottir
Michael Doherty
David L Morris
Massimo Mangino
Agu Tamm
Sally A Doherty
Kalle Kisand
Irina Kerna
Ann Tamm
Margaret Wheeler
Rose A Maciewicz
Weiya Zhang
Kenneth R Muir
Elaine M Dennison
Deborah J Hart
Sarah Metrustry
Ingileif Jonsdottir
Gudbjorn F Jonsson
Helgi Jonsson
Thorvaldur Ingvarsson
Cyrus Cooper
Timothy J Vyse
Tim D Spector
Kari Stefansson
Nigel K Arden
author_facet Ana M Valdes
Unnur Styrkarsdottir
Michael Doherty
David L Morris
Massimo Mangino
Agu Tamm
Sally A Doherty
Kalle Kisand
Irina Kerna
Ann Tamm
Margaret Wheeler
Rose A Maciewicz
Weiya Zhang
Kenneth R Muir
Elaine M Dennison
Deborah J Hart
Sarah Metrustry
Ingileif Jonsdottir
Gudbjorn F Jonsson
Helgi Jonsson
Thorvaldur Ingvarsson
Cyrus Cooper
Timothy J Vyse
Tim D Spector
Kari Stefansson
Nigel K Arden
author_sort Ana M Valdes
collection DOAJ
description Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r(2) = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r(2)<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.
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spelling doaj-art-e96f0801c8564122b6eb09219f2f8b712025-08-20T02:33:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2337110.1371/journal.pone.0023371Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.Ana M ValdesUnnur StyrkarsdottirMichael DohertyDavid L MorrisMassimo ManginoAgu TammSally A DohertyKalle KisandIrina KernaAnn TammMargaret WheelerRose A MaciewiczWeiya ZhangKenneth R MuirElaine M DennisonDeborah J HartSarah MetrustryIngileif JonsdottirGudbjorn F JonssonHelgi JonssonThorvaldur IngvarssonCyrus CooperTimothy J VyseTim D SpectorKari StefanssonNigel K ArdenOsteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r(2) = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r(2)<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023371&type=printable
spellingShingle Ana M Valdes
Unnur Styrkarsdottir
Michael Doherty
David L Morris
Massimo Mangino
Agu Tamm
Sally A Doherty
Kalle Kisand
Irina Kerna
Ann Tamm
Margaret Wheeler
Rose A Maciewicz
Weiya Zhang
Kenneth R Muir
Elaine M Dennison
Deborah J Hart
Sarah Metrustry
Ingileif Jonsdottir
Gudbjorn F Jonsson
Helgi Jonsson
Thorvaldur Ingvarsson
Cyrus Cooper
Timothy J Vyse
Tim D Spector
Kari Stefansson
Nigel K Arden
Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
PLoS ONE
title Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
title_full Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
title_fullStr Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
title_full_unstemmed Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
title_short Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
title_sort large scale replication study of the association between hla class ii btnl2 variants and osteoarthritis of the knee in european descent populations
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023371&type=printable
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