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Title:
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci | Nature Genetics
Description:
Eli Stahl and colleagues report results of a genome-wide association study meta-analysis and replication study for rheumatoid arthritis. Their work identifies several new risk loci and highlights genetic overlap with other autoimmune diseases. To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 Γ 10β8) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
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headline:Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci
description:Eli Stahl and colleagues report results of a genome-wide association study meta-analysis and replication study for rheumatoid arthritis. Their work identifies several new risk loci and highlights genetic overlap with other autoimmune diseases. To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 ΓΒ 10Γ’ΒΒ8) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
datePublished:2010-05-09T00:00:00Z
dateModified:2010-05-09T00:00:00Z
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Genetic predisposition to disease
Genome-wide association studies
Rheumatoid arthritis
Risk factors
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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headline:Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci
description:Eli Stahl and colleagues report results of a genome-wide association study meta-analysis and replication study for rheumatoid arthritis. Their work identifies several new risk loci and highlights genetic overlap with other autoimmune diseases. To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 ΓΒ 10Γ’ΒΒ8) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
datePublished:2010-05-09T00:00:00Z
dateModified:2010-05-09T00:00:00Z
pageStart:508
pageEnd:514
sameAs:https://doi.org/10.1038/ng.582
keywords:
Genetic predisposition to disease
Genome-wide association studies
Rheumatoid arthritis
Risk factors
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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name:Arthritis Research UK Epidemiology Unit, Stopford Building, The University of Manchester, Manchester, UK
name:National Institute for Health Research-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
name:Department of Medicine, Rheumatology Unit, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
name:Department of Rheumatology and Clinical Immunology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
name:Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
name:Division of Applied Medicine, Musculoskeletal and Genetics Section, University of Aberdeen, Aberdeen, UK
name:Genome Institute of Singapore, Singapore
name:Rowe Program in Genetics, University of California at Davis, Davis, USA
name:Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, USA
name:Clinical and Academic Rheumatology, Kings College Hospital National Health Service Foundation Trust, Denmark Hill, London, UK.,
name:Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
name:Arthritis Research UK Epidemiology Unit, Stopford Building, The University of Manchester, Manchester, UK
name:Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
name:Department of Rheumatology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands
name:Sanquin Research Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
name:Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
name:Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, USA
name:School of Medicine and Biomedical Sciences, Sheffield University, Sheffield, UK
name:Sanquin Research Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
name:Jan van Breemen Institute, Amsterdam, The Netherlands
name:University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK
name:Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
name:Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, USA
name:Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
name:Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
name:Celera, Alameda, USA
name:Roche Diagnostics, Pleasanton, USA
name:Arthritis Research UK Epidemiology Unit, Stopford Building, The University of Manchester, Manchester, UK
name:Department of Medicine, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, Canada
name:The Feinstein Institute for Medical Research, North ShoreΓ’ΒΒLong Island Jewish Health System, Manhasset, USA
name:Department of Medicine, Rheumatology Unit, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
name:Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, USA
name:Broad Institute, Cambridge, USA
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