Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
Tsoi LC, Spain SL, Ellinghaus E, Stuart PE, Capon F, Knight J, Tejasvi T, Kang HM, Allen MH, Lambert S, Stoll SW, Weidinger S, Gudjonsson JE, Koks S, Kingo K, Esko T, Das S, Metspalu A, Weichenthal M, Enerback C, Krueger GG, Voorhees JJ, Chandran V, Rosen CF, Rahman P, Gladman DD, Reis A, Nair RP, Franke A, Barker JNWN, Abecasis GR, Trembath RC, Elder JT (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 6
Pages Range: 7001
DOI: 10.1038/ncomms8001
Abstract
Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.
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Involved external institutions
Memorial University of Newfoundland (MUN)
Canada (CA)
University of Michigan
United States (USA) (US)
Queen Mary University of London
United Kingdom (GB)
King’s College London
United Kingdom (GB)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
University of Toronto
Canada (CA)
University of Utah
United States (USA) (US)
Linköpings universitet / Linköping University
Sweden (SE)
University of Tartu
Estonia (EE)
Centre for Addiction and Mental Health (CAMH)
Canada (CA)
Canada (CA)
University of Michigan
United States (USA) (US)
Queen Mary University of London
United Kingdom (GB)
King’s College London
United Kingdom (GB)
Christian-Albrechts-Universität zu Kiel
Germany (DE)
University of Toronto
Canada (CA)
University of Utah
United States (USA) (US)
Linköpings universitet / Linköping University
Sweden (SE)
University of Tartu
Estonia (EE)
Centre for Addiction and Mental Health (CAMH)
Canada (CA)
How to cite
APA:
Tsoi, L.C., Spain, S.L., Ellinghaus, E., Stuart, P.E., Capon, F., Knight, J.,... Elder, J.T. (2015). Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nature Communications, 6, 7001. https://doi.org/10.1038/ncomms8001
MLA:
Tsoi, Lam C., et al. "Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci." Nature Communications 6 (2015): 7001.
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