TY - JOUR
T1 - PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis
T2 - Evidence for a further PSA-specific risk locus
AU - Bowes, John
AU - Loehr, Sabine
AU - Budu-Aggrey, Ashley
AU - Uebe, Steffen
AU - Bruce, Ian N.
AU - Feletar, Marie
AU - Marzo-Ortega, Helena
AU - Helliwell, Philip
AU - Ryan, Anthony W.
AU - Kane, David
AU - Korendowych, Eleanor
AU - Alenius, Gerd Marie
AU - Giardina, Emiliano
AU - Packham, Jonathan
AU - McManus, Ross
AU - Fitzgerald, Oliver
AU - Brown, Matthew A.
AU - Behrens, Frank
AU - Burkhardt, Harald
AU - McHugh, Neil
AU - Huffmeier, Ulrike
AU - Ho, Pauline
AU - Reis, Andre
AU - Barton, Anne
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. Methods: A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10-4) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. Results: We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10-9, OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10-4). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10-9). Conclusions: For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.
AB - Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. Methods: A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10-4) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. Results: We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10-9, OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10-4). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10-9). Conclusions: For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.
UR - http://www.scopus.com/inward/record.url?scp=84942865699&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2014-207187
DO - 10.1136/annrheumdis-2014-207187
M3 - Article (Academic Journal)
C2 - 25923216
AN - SCOPUS:84942865699
VL - 74
SP - 1882
EP - 1885
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 10
ER -