PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus

John Bowes, Sabine Loehr, Ashley Budu-Aggrey, Steffen Uebe, Ian N Bruce, Marie Feletar, Helena Marzo-Ortega, Philip Helliwell, Anthony W Ryan, David Kane, Eleanor Korendowych, Gerd-Marie Alenius, Emiliano Giardina, Jonathan Packham, Ross McManus, Oliver FitzGerald, Matthew A Brown, Frank Behrens, Harald Burkhardt, Neil McHugh & 4 others Ulrike Huffmeier, Pauline Ho, Andre Reis, Anne Barton

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Abstract

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.

LanguageEnglish
Pages1882-1885
Number of pages4
JournalAnnals of the Rheumatic Diseases
Volume74
Issue number10
Early online date28 Apr 2015
DOIs
StatusPublished - Oct 2015

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Psoriatic Arthritis
Psoriasis
Genes
Polymorphism
Nucleotides
Genome
Single Nucleotide Polymorphism
Genetic Loci
Genetic Predisposition to Disease
Arthritis
Meta-Analysis

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Bowes, J., Loehr, S., Budu-Aggrey, A., Uebe, S., Bruce, I. N., Feletar, M., ... Barton, A. (2015). PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus. Annals of the Rheumatic Diseases, 74 (10), 1882-1885. DOI: 10.1136/annrheumdis-2014-207187

PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis : evidence for a further PsA-specific risk locus. / Bowes, John; Loehr, Sabine; Budu-Aggrey, Ashley; Uebe, Steffen; Bruce, Ian N; Feletar, Marie; Marzo-Ortega, Helena; Helliwell, Philip; Ryan, Anthony W; Kane, David; Korendowych, Eleanor; Alenius, Gerd-Marie; Giardina, Emiliano; Packham, Jonathan; McManus, Ross; FitzGerald, Oliver; Brown, Matthew A; Behrens, Frank; Burkhardt, Harald; McHugh, Neil; Huffmeier, Ulrike; Ho, Pauline; Reis, Andre; Barton, Anne.

In: Annals of the Rheumatic Diseases, Vol. 74 , No. 10, 10.2015, p. 1882-1885.

Research output: Contribution to journalArticle

Bowes, J, Loehr, S, Budu-Aggrey, A, Uebe, S, Bruce, IN, Feletar, M, Marzo-Ortega, H, Helliwell, P, Ryan, AW, Kane, D, Korendowych, E, Alenius, G-M, Giardina, E, Packham, J, McManus, R, FitzGerald, O, Brown, MA, Behrens, F, Burkhardt, H, McHugh, N, Huffmeier, U, Ho, P, Reis, A & Barton, A 2015, 'PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus' Annals of the Rheumatic Diseases, vol 74 , no. 10, pp. 1882-1885. DOI: 10.1136/annrheumdis-2014-207187
Bowes, John ; Loehr, Sabine ; Budu-Aggrey, Ashley ; Uebe, Steffen ; Bruce, Ian N ; Feletar, Marie ; Marzo-Ortega, Helena ; Helliwell, Philip ; Ryan, Anthony W ; Kane, David ; Korendowych, Eleanor ; Alenius, Gerd-Marie ; Giardina, Emiliano ; Packham, Jonathan ; McManus, Ross ; FitzGerald, Oliver ; Brown, Matthew A ; Behrens, Frank ; Burkhardt, Harald ; McHugh, Neil ; Huffmeier, Ulrike ; Ho, Pauline ; Reis, Andre ; Barton, Anne. / PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis : evidence for a further PsA-specific risk locus. In: Annals of the Rheumatic Diseases. 2015 ; Vol. 74 , No. 10. pp. 1882-1885
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abstract = "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.",
author = "John Bowes and Sabine Loehr and Ashley Budu-Aggrey and Steffen Uebe and Bruce, {Ian N} and Marie Feletar and Helena Marzo-Ortega and Philip Helliwell and Ryan, {Anthony W} and David Kane and Eleanor Korendowych and Gerd-Marie Alenius and Emiliano Giardina and Jonathan Packham and Ross McManus and Oliver FitzGerald and Brown, {Matthew A} and Frank Behrens and Harald Burkhardt and Neil McHugh and Ulrike Huffmeier and Pauline Ho and Andre Reis and Anne Barton",
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TY - JOUR

T1 - PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis

T2 - Annals of the Rheumatic Diseases

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

Y1 - 2015/10

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://dx.doi.org/10.1136/annrheumdis-2014-207187

U2 - 10.1136/annrheumdis-2014-207187

DO - 10.1136/annrheumdis-2014-207187

M3 - Article

VL - 74

SP - 1882

EP - 1885

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 10

ER -