Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture

Stuart PE, Nair RP, Tsoi LC, Tejasvi T, Das S, Kang HM, Ellinghaus E, Chandran V, Callis-Duffin K, Ike R, Li Y, Wen X, Enerback C, Gudjonsson JE, Koks S, Kingo K, Esko T, Mrowietz U, Reis A, Wichmann HE, Gieger C, Hoffmann P, Noethen MM, Winkelmann J, Kunz M, Moreta EG, Mease PJ, Ritchlin CT, Bowcock AM, Krueger GG, Lim HW, Weidinger S, Weichenthal M, Voorhees JJ, Rahman P, Gregersen PK, Franke A, Gladman DD, Abecasis GR, Elder JT (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 97

Pages Range: 816-36

Journal Issue: 6

DOI: 10.1016/j.ajhg.2015.10.019

Abstract

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

Authors with CRIS profile

Involved external institutions

University of Toronto Canada (CA) University of Tartu Estonia (EE) Swedish Medical Center United States (USA) (US) Memorial University of Newfoundland (MUN) Canada (CA) University of Michigan United States (USA) (US) Christian-Albrechts-Universität zu Kiel Germany (DE) Northwell Health United States (USA) (US) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Henry Ford Health System (HFHS) United States (USA) (US) University of Utah United States (USA) (US) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) University of Rochester (UR) United States (USA) (US) Saint Paul Rheumatology United States (USA) (US) Universität Leipzig Germany (DE) Technische Universität München (TUM) Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE) Linköping University Sweden (SE)

How to cite

APA:

Stuart, P.E., Nair, R.P., Tsoi, L.C., Tejasvi, T., Das, S., Kang, H.M.,... Elder, J.T. (2015). Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture. American Journal of Human Genetics, 97(6), 816-36. https://doi.org/10.1016/j.ajhg.2015.10.019

MLA:

Stuart, Philip E., et al. "Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture." American Journal of Human Genetics 97.6 (2015): 816-36.

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