Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2.
Psoriasis is a multifactorial skin disease characterized by epidermal hyperproliferation and chronic inflammation, the most common form of which is psoriasis vulgaris (PsV). We present a genome-wide association analysis of 2,339,118 SNPs in 472 PsV cases and 1,146 controls from Germany, with follow-up of the 147 most significant SNPs in 2,746 PsV cases and 4,140 controls from three independent replication panels. We identified an association at TRAF3IP2 on 6q21 and genotyped two SNPs at this locus in two additional replication panels (the combined discovery and replication panels consisted of 6,487 cases and 8,037 controls; combined P = 2.36 × 10⁻¹⁰ for rs13210247 and combined P = 1.24 × 10⁻¹⁶ for rs33980500). About 15% of psoriasis cases develop psoriatic arthritis (PsA). A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10⁻¹² for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA. TRAF3IP2 encodes a protein involved in IL-17 signaling and which interacts with members of the Rel/NF-κB transcription factor family.
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
Eva
E
Ellinghaus
David
D
Ellinghaus
Philip E
PE
Stuart
Rajan P
RP
Nair
Sophie
S
Debrus
John V
JV
Raelson
Majid
M
Belouchi
Hélène
H
Fournier
Claudia
C
Reinhard
Jun
J
Ding
Yun
Y
Li
Trilokraj
T
Tejasvi
Johann
J
Gudjonsson
Stefan W
SW
Stoll
John J
JJ
Voorhees
Sylviane
S
Lambert
Stephan
S
Weidinger
Bernadette
B
Eberlein
Manfred
M
Kunz
Proton
P
Rahman
Dafna D
DD
Gladman
Christian
C
Gieger
H Erich
HE
Wichmann
Tom H
TH
Karlsen
Gabriele
G
Mayr
Mario
M
Albrecht
Dieter
D
Kabelitz
Ulrich
U
Mrowietz
Gonçalo R
GR
Abecasis
James T
JT
Elder
Stefan
S
Schreiber
Michael
M
Weichenthal
Andre
A
Franke
D048868:Adaptor Proteins, Signal Transducing; D015535:Arthritis, Psoriatic / Q000209:etiology / Q000235:genetics; D002896:Chromosomes, Human, Pair 6; D004200:Diseases in Twins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D035781:Siblings; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D015236:HLA-C Antigens; D007378:Interleukins; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins