Journal
NATURE GENETICS
Volume 42, Issue 11, Pages 996-U118Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.688
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Funding
- Interdisciplinary Centre for Clinical Research of the University of Erlangen-Nuremberg [IZKF B32/A8]
- Helmholtz Center Munich
- German Federal Ministry of Education and Research (BMBF)
- German National Genome Research Network [NGFN-2, NGFNPlus: 01GS0823]
- Munich Center of Health Sciences (MC Health)
- National Institute for Health Research
- Manchester Biomedical Research Centre
- Science Foundation Ireland
- Arthritis Research
- Wyeth Pharma GmbH, Germany
- ADIPSO (Association for the Defense of Psoriasis Patients)
- Wellcome Trust [076113]
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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 x 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 x 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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