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

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

149 Citations (Scopus)

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
Pages (from-to)	6046
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7046
Publication status	Published - 5 Feb 2015

Keywords

Adult
Aged
Aged, 80 and over
Alleles
Arthritis, Psoriatic
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Case-Control Studies
Chromatin
Chromosomes, Human, Pair 5
Female
Genetic Predisposition to Disease
Genotype
Genotyping Techniques
Histocompatibility Antigens Class I
Humans
Immunologic Memory
Male
Microarray Analysis
Middle Aged
Polymorphism, Single Nucleotide
Psoriasis
Quantitative Trait Loci
Receptors, Interleukin
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms7046

Handle.net

Persistent link

149 Citations
1 Article (Academic Journal)

Corrigendum: Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis
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. & Korendowych, E. & 12 others, Alenius, G.-M., Giardina, E., Packham, J., McManus, R., FitzGerald, O., McHugh, N., Brown, M. A., Ho, P., Behrens, F., Burkhardt, H., Reis, A. & Barton, A., 6 Jul 2015, In: Nature Communications. 6, p. 7741 1 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-review

7 Citations (Scopus)

Cite this

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

@article{734f1d10dcc24d59868a7de0cca33043,

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.",

keywords = "Adult, Aged, Aged, 80 and over, Alleles, Arthritis, Psoriatic, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Case-Control Studies, Chromatin, Chromosomes, Human, Pair 5, Female, Genetic Predisposition to Disease, Genotype, Genotyping Techniques, Histocompatibility Antigens Class I, Humans, Immunologic Memory, Male, Microarray Analysis, Middle Aged, Polymorphism, Single Nucleotide, Psoriasis, Quantitative Trait Loci, Receptors, Interleukin, Journal Article, Research Support, Non-U.S. Gov't",

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 Gerd-Marie Alenius 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",

year = "2015",

month = feb,

day = "5",

doi = "10.1038/ncomms7046",

language = "English",

volume = "6",

pages = "6046",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer Nature",

}

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, G-M, 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, pp. 6046. https://doi.org/10.1038/ncomms7046

TY - JOUR

T1 - Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis

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 - 2015/2/5

Y1 - 2015/2/5

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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Arthritis, Psoriatic

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Case-Control Studies

KW - Chromatin

KW - Chromosomes, Human, Pair 5

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Genotyping Techniques

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Immunologic Memory

KW - Male

KW - Microarray Analysis

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Psoriasis

KW - Quantitative Trait Loci

KW - Receptors, Interleukin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ncomms7046

DO - 10.1038/ncomms7046

M3 - Article (Academic Journal)

C2 - 25651891

SN - 2041-1723

VL - 6

SP - 6046

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Handle.net

Fingerprint

Research output

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

Cite this