TY - JOUR
T1 - Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture
AU - Stuart, Philip E.
AU - Nair, Rajan P.
AU - Tsoi, Lam C.
AU - Tejasvi, Trilokraj
AU - Das, Sayantan
AU - Kang, Hyun Min
AU - Ellinghaus, Eva
AU - Chandran, Vinod
AU - Callis-Duffin, Kristina
AU - Ike, Robert
AU - Li, Yanming
AU - Wen, Xiaoquan
AU - Enerbäck, Charlotta
AU - Gudjonsson, Johann E.
AU - Kõks, Sulev
AU - Kingo, Külli
AU - Esko, Tõnu
AU - Mrowietz, Ulrich
AU - Reis, Andre
AU - Wichmann, H. Erich
AU - Gieger, Christian
AU - Hoffmann, Per
AU - Nöthen, Markus M.
AU - Winkelmann, Juliane
AU - Kunz, Manfred
AU - Moreta, Elvia G.
AU - Mease, Philip J.
AU - Ritchlin, Christopher T.
AU - Bowcock, Anne M.
AU - Krueger, Gerald G.
AU - Lim, Henry W.
AU - Weidinger, Stephan
AU - Weichenthal, Michael
AU - Voorhees, John J.
AU - Rahman, Proton
AU - Gregersen, Peter K.
AU - Franke, Andre
AU - Gladman, Dafna D.
AU - Abecasis, Gonçalo R.
AU - Elder, James T.
N1 - Publisher Copyright:
© 2015 The American Society of Human Genetics.
PY - 2015/12/3
Y1 - 2015/12/3
N2 - 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.
AB - 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.
KW - genome-wide association study
KW - joint diseases
KW - psoriasis
KW - psoriatic arthritis
KW - skin diseases
UR - http://www.scopus.com/inward/record.url?scp=84952638740&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2015.10.019
DO - 10.1016/j.ajhg.2015.10.019
M3 - Article
C2 - 26626624
AN - SCOPUS:84952638740
SN - 0002-9297
VL - 97
SP - 816
EP - 836
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -