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Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

BACKGROUND: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50–60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with...

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Autores principales: Plant, Darren, Flynn, Edward, Mbarek, Hamdi, Dieudé, Philippe, Cornelis, François, Ärlestig, Lisbeth, Dahlqvist, Solbritt Rantapää, Goulielmos, George, Boumpas, Dimitrios T, Sidiropoulos, Prodromos, Johansen, Julia S, Ørnbjerg, Lykke M, Hetland, Merete Lund, Klareskog, Lars, Filer, Andrew, Buckley, Christopher D, Raza, Karim, Witte, Torsten, Schmidt, Reinhold E, Worthington, Jane
Formato: Texto
Lenguaje:English
Publicado: BMJ Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938898/
https://www.ncbi.nlm.nih.gov/pubmed/20498205
http://dx.doi.org/10.1136/ard.2009.121020
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author Plant, Darren
Flynn, Edward
Mbarek, Hamdi
Dieudé, Philippe
Cornelis, François
Ärlestig, Lisbeth
Dahlqvist, Solbritt Rantapää
Goulielmos, George
Boumpas, Dimitrios T
Sidiropoulos, Prodromos
Johansen, Julia S
Ørnbjerg, Lykke M
Hetland, Merete Lund
Klareskog, Lars
Filer, Andrew
Buckley, Christopher D
Raza, Karim
Witte, Torsten
Schmidt, Reinhold E
Worthington, Jane
author_facet Plant, Darren
Flynn, Edward
Mbarek, Hamdi
Dieudé, Philippe
Cornelis, François
Ärlestig, Lisbeth
Dahlqvist, Solbritt Rantapää
Goulielmos, George
Boumpas, Dimitrios T
Sidiropoulos, Prodromos
Johansen, Julia S
Ørnbjerg, Lykke M
Hetland, Merete Lund
Klareskog, Lars
Filer, Andrew
Buckley, Christopher D
Raza, Karim
Witte, Torsten
Schmidt, Reinhold E
Worthington, Jane
author_sort Plant, Darren
collection PubMed
description BACKGROUND: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50–60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. OBJECTIVES: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. METHODS: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. RESULTS: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. CONCLUSIONS: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.
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spelling pubmed-29388982010-09-15 Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers Plant, Darren Flynn, Edward Mbarek, Hamdi Dieudé, Philippe Cornelis, François Ärlestig, Lisbeth Dahlqvist, Solbritt Rantapää Goulielmos, George Boumpas, Dimitrios T Sidiropoulos, Prodromos Johansen, Julia S Ørnbjerg, Lykke M Hetland, Merete Lund Klareskog, Lars Filer, Andrew Buckley, Christopher D Raza, Karim Witte, Torsten Schmidt, Reinhold E Worthington, Jane Ann Rheum Dis Basic and Translational Research BACKGROUND: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50–60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. OBJECTIVES: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. METHODS: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. RESULTS: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. CONCLUSIONS: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained. BMJ Group 2010-08-01 /pmc/articles/PMC2938898/ /pubmed/20498205 http://dx.doi.org/10.1136/ard.2009.121020 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.
spellingShingle Basic and Translational Research
Plant, Darren
Flynn, Edward
Mbarek, Hamdi
Dieudé, Philippe
Cornelis, François
Ärlestig, Lisbeth
Dahlqvist, Solbritt Rantapää
Goulielmos, George
Boumpas, Dimitrios T
Sidiropoulos, Prodromos
Johansen, Julia S
Ørnbjerg, Lykke M
Hetland, Merete Lund
Klareskog, Lars
Filer, Andrew
Buckley, Christopher D
Raza, Karim
Witte, Torsten
Schmidt, Reinhold E
Worthington, Jane
Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
title Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
title_full Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
title_fullStr Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
title_full_unstemmed Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
title_short Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
title_sort investigation of potential non-hla rheumatoid arthritis susceptibility loci in a european cohort increases the evidence for nine markers
topic Basic and Translational Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938898/
https://www.ncbi.nlm.nih.gov/pubmed/20498205
http://dx.doi.org/10.1136/ard.2009.121020
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