Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis

John Bowes; Ashley Budu-Aggrey; Ulrike Huffmeier; Steffen Uebe; Kathryn Steel; Harry L. Hebert; Chris Wallace; Jonathan Massey; Ian N. Bruce; James Bluett; Marie Feletar; Ann W. Morgan; Helena Marzo-Ortega; Gary Donohoe; Derek W. Morris; Philip Helliwell; Anthony W. Ryan; David Kane; Richard B. Warren; Eleanor Korendowych; Gerd Marie Alenius; Emiliano Giardina; Jonathan Packham; Ross McManus; Oliver Fitzgerald; Neil McHugh; Matthew A. Brown; Pauline Ho; Frank Behrens; Harald Burkhardt; Andre Reis; Anne Barton

doi:10.1038/ncomms7046

Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis

John Bowes, Ashley Budu-Aggrey, Ulrike Huffmeier, Steffen Uebe, Kathryn Steel, Harry L. Hebert, Chris Wallace, Jonathan Massey, Ian N. Bruce, James Bluett, Marie Feletar, Ann W. Morgan, Helena Marzo-Ortega, Gary Donohoe, Derek W. Morris, Philip Helliwell, Anthony W. Ryan, David Kane, Richard B. Warren, Eleanor KorendowychGerd Marie Alenius, Emiliano Giardina, Jonathan Packham, Ross McManus, Oliver Fitzgerald, Neil McHugh, Matthew A. Brown, Pauline Ho, Frank Behrens, Harald Burkhardt, Andre Reis, Anne Barton

Fondazione Santa Lucia

Research output: Contribution to journal › Article › peer-review

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8⁺ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

Original language	English
Article number	6046
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7046
Publication status	Published - 2015

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Chemistry(all)
Physics and Astronomy(all)

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Bowes, J., Budu-Aggrey, A., Huffmeier, U., Uebe, S., Steel, K., Hebert, H. L., Wallace, C., Massey, J., Bruce, I. N., Bluett, J., Feletar, M., Morgan, A. W., Marzo-Ortega, H., Donohoe, G., Morris, D. W., Helliwell, P., Ryan, A. W., Kane, D., Warren, R. B., ... Barton, A. (2015). Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nature Communications, 6, [6046]. https://doi.org/10.1038/ncomms7046

Bowes, J, Budu-Aggrey, A, Huffmeier, U, Uebe, S, Steel, K, Hebert, HL, Wallace, C, Massey, J, Bruce, IN, Bluett, J, Feletar, M, Morgan, AW, Marzo-Ortega, H, Donohoe, G, Morris, DW, Helliwell, P, Ryan, AW, Kane, D, Warren, RB, Korendowych, E, Alenius, GM, Giardina, E, Packham, J, McManus, R, Fitzgerald, O, McHugh, N, Brown, MA, Ho, P, Behrens, F, Burkhardt, H, Reis, A & Barton, A 2015, 'Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis', Nature Communications, vol. 6, 6046. https://doi.org/10.1038/ncomms7046

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title = "Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis",

abstract = "Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.",

author = "John Bowes and Ashley Budu-Aggrey and Ulrike Huffmeier and Steffen Uebe and Kathryn Steel and Hebert, {Harry L.} and Chris Wallace and Jonathan Massey and Bruce, {Ian N.} and James Bluett and Marie Feletar and Morgan, {Ann W.} and Helena Marzo-Ortega and Gary Donohoe and Morris, {Derek W.} and Philip Helliwell and Ryan, {Anthony W.} and David Kane and Warren, {Richard B.} and Eleanor Korendowych and Alenius, {Gerd Marie} and Emiliano Giardina and Jonathan Packham and Ross McManus and Oliver Fitzgerald and Neil McHugh and Brown, {Matthew A.} and Pauline Ho and Frank Behrens and Harald Burkhardt and Andre Reis and Anne Barton",

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AU - Bowes, John

AU - Budu-Aggrey, Ashley

AU - Huffmeier, Ulrike

AU - Uebe, Steffen

AU - Steel, Kathryn

AU - Hebert, Harry L.

AU - Wallace, Chris

AU - Massey, Jonathan

AU - Bruce, Ian N.

AU - Bluett, James

AU - Feletar, Marie

AU - Morgan, Ann W.

AU - Marzo-Ortega, Helena

AU - Donohoe, Gary

AU - Morris, Derek W.

AU - Helliwell, Philip

AU - Ryan, Anthony W.

AU - Kane, David

AU - Warren, Richard B.

AU - Korendowych, Eleanor

AU - Alenius, Gerd Marie

AU - Giardina, Emiliano

AU - Packham, Jonathan

AU - McManus, Ross

AU - Fitzgerald, Oliver

AU - McHugh, Neil

AU - Brown, Matthew A.

AU - Ho, Pauline

AU - Behrens, Frank

AU - Burkhardt, Harald

AU - Reis, Andre

AU - Barton, Anne

PY - 2015

Y1 - 2015

N2 - Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

AB - Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

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Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis

Abstract

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