Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

U Huffmeier; S Uebe; A B Ekici; J Bowes; E Giardina; E Korendowych; K Juneblad; M Apel; R McManus; P Ho; I N Bruce; A W Ryan; F Behrens; J Lascorz; B Bohm; H Traupe; J Lohmann; C Gieger; H E Wichmann; C Herold; M Steffens; L Klareskog; T F Wienker; O FitzGerald; G M Alenius; Neil J McHugh; G Novelli; H Burkhardt; A Barton; A Reis

doi:10.1038/ng.688

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

U Huffmeier, S Uebe, A B Ekici, J Bowes, E Giardina, E Korendowych, K Juneblad, M Apel, R McManus, P Ho, I N Bruce, A W Ryan, F Behrens, J Lascorz, B Bohm, H Traupe, J Lohmann, C Gieger, H E Wichmann, C HeroldM Steffens, L Klareskog, T F Wienker, O FitzGerald, G M Alenius, Neil J McHugh, G Novelli, H Burkhardt, A Barton, A Reis

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Abstract

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 x 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

Original language	English
Pages (from-to)	996-999
Number of pages	4
Journal	Nature Genetics
Volume	42
Issue number	11
Early online date	16 Oct 2010
DOIs	https://doi.org/10.1038/ng.688
Publication status	Published - Nov 2010

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Huffmeier, U., Uebe, S., Ekici, A. B., Bowes, J., Giardina, E., Korendowych, E., Juneblad, K., Apel, M., McManus, R., Ho, P., Bruce, I. N., Ryan, A. W., Behrens, F., Lascorz, J., Bohm, B., Traupe, H., Lohmann, J., Gieger, C., Wichmann, H. E., ... Reis, A. (2010). Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nature Genetics, 42(11), 996-999. https://doi.org/10.1038/ng.688

Huffmeier, U, Uebe, S, Ekici, AB, Bowes, J, Giardina, E, Korendowych, E, Juneblad, K, Apel, M, McManus, R, Ho, P, Bruce, IN, Ryan, AW, Behrens, F, Lascorz, J, Bohm, B, Traupe, H, Lohmann, J, Gieger, C, Wichmann, HE, Herold, C, Steffens, M, Klareskog, L, Wienker, TF, FitzGerald, O, Alenius, GM, McHugh, NJ, Novelli, G, Burkhardt, H, Barton, A & Reis, A 2010, 'Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis', Nature Genetics, vol. 42, no. 11, pp. 996-999. https://doi.org/10.1038/ng.688

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title = "Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis",

abstract = "Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 x 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.",

author = "U Huffmeier and S Uebe and Ekici, {A B} and J Bowes and E Giardina and E Korendowych and K Juneblad and M Apel and R McManus and P Ho and Bruce, {I N} and Ryan, {A W} and F Behrens and J Lascorz and B Bohm and H Traupe and J Lohmann and C Gieger and Wichmann, {H E} and C Herold and M Steffens and L Klareskog and Wienker, {T F} and O FitzGerald and Alenius, {G M} and McHugh, {Neil J} and G Novelli and H Burkhardt and A Barton and A Reis",

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AU - Huffmeier, U

AU - Uebe, S

AU - Ekici, A B

AU - Bowes, J

AU - Giardina, E

AU - Korendowych, E

AU - Juneblad, K

AU - Apel, M

AU - McManus, R

AU - Ho, P

AU - Bruce, I N

AU - Ryan, A W

AU - Behrens, F

AU - Lascorz, J

AU - Bohm, B

AU - Traupe, H

AU - Lohmann, J

AU - Gieger, C

AU - Wichmann, H E

AU - Herold, C

AU - Steffens, M

AU - Klareskog, L

AU - Wienker, T F

AU - FitzGerald, O

AU - Alenius, G M

AU - McHugh, Neil J

AU - Novelli, G

AU - Burkhardt, H

AU - Barton, A

AU - Reis, A

PY - 2010/11

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N2 - Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 x 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

AB - Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 x 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

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