Risk variants for psoriasis vulgaris in a large case-control collection and association with clinical subphenotypes.
Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.
Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona 08035, Spain.
Antonio
A
Julià
Raül
R
Tortosa
José Manuel
JM
Hernanz
Juan D
JD
Cañete
Eduardo
E
Fonseca
Carlos
C
Ferrándiz
Pablo
P
Unamuno
Lluís
L
Puig
José Luís
JL
Fernández-Sueiro
Raimon
R
Sanmartí
Jesús
J
Rodríguez
Jordi
J
Gratacós
Esteban
E
Dauden
José Luís
JL
Sánchez-Carazo
José Luís
JL
López-Estebaranz
David
D
Moreno-Ramírez
Rubén
R
Queiró
Carlos
C
Montilla
Juan Carlos
JC
Torre-Alonso
José Javier
JJ
Pérez-Venegas
Francisco
F
Vanaclocha
Enrique
E
Herrera
Santiago
S
Muñoz-Fernández
Carlos
C
González
Daniel
D
Roig
Alba
A
Erra
Isabel
I
Acosta
Antonio
A
Fernández-Nebro
Pedro
P
Zarco
Arnald
A
Alonso
María
M
López-Lasanta
Andrés
A
García-Montero
Josep Lluís
JL
Gelpí
Devin
D
Absher
Sara
S
Marsal
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D008297:Male; D015778:Minor Histocompatibility Antigens; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics*; D012867:Skin / Q000276:immunology / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; C553748:COG6 protein, human; D015236:HLA-C Antigens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human