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Title:
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis | Nature Genetics
Description:
André Reis and colleagues report a genome-wide association study identifying a susceptibility locus at TRAF3IP2 for psoriatic arthritis and psoriasis. Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10−17). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10−3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10−20, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
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headline:Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
description:André Reis and colleagues report a genome-wide association study identifying a susceptibility locus at TRAF3IP2 for psoriatic arthritis and psoriasis. Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 à 10â17). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 à 10â3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 à 10â20, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
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Genome-wide association studies
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headline:Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
description:André Reis and colleagues report a genome-wide association study identifying a susceptibility locus at TRAF3IP2 for psoriatic arthritis and psoriasis. Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 à 10â17). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 à 10â3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 à 10â20, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
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Epidemiology
Genome-wide association studies
Psoriasis
Psoriatic arthritis
Biomedicine
general
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Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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name:Nature Genetics
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1546-1718
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address:
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name:Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany
name:Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany
name:Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
name:Department of Biopathology, Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome 'Tor Vergata' and Fondazione PTV 'Policlinico Tor Vergata', Rome, Italy
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