Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease

Stephen Eyre, Anne Hinks, John Bowes, Edward Flynn, Paul Martin, Anthony G. Wilson, Ann W. Morgan, Paul Emery, Sophia Steer, Lynne J Hocking, David M. Reid, Pille Harrison, Paul Wordsworth, Wendy Thomson, Jane Worthington, Anne Barton, BIRAC consortium

Research output: Contribution to journalArticle

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Abstract

Introduction: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD).

Methods: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant.

Results: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 x 10(-4)). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold.

Conclusions: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation.

Original languageEnglish
Article numberR175
Number of pages6
JournalArthritis Research & Therapy
Volume12
Issue number5
DOIs
Publication statusPublished - 20 Sep 2010

Keywords

  • juvenile idiopathic arthritis
  • genome-wide association
  • risk
  • loci
  • classification
  • expression
  • common

Cite this

Overlapping genetic susceptibility variants between three autoimmune disorders : rheumatoid arthritis, type 1 diabetes and coeliac disease. / Eyre, Stephen; Hinks, Anne; Bowes, John; Flynn, Edward; Martin, Paul; Wilson, Anthony G.; Morgan, Ann W.; Emery, Paul; Steer, Sophia; Hocking, Lynne J; Reid, David M.; Harrison, Pille; Wordsworth, Paul; Thomson, Wendy; Worthington, Jane; Barton, Anne; BIRAC consortium.

In: Arthritis Research & Therapy, Vol. 12, No. 5, R175, 20.09.2010.

Research output: Contribution to journalArticle

Eyre, S, Hinks, A, Bowes, J, Flynn, E, Martin, P, Wilson, AG, Morgan, AW, Emery, P, Steer, S, Hocking, LJ, Reid, DM, Harrison, P, Wordsworth, P, Thomson, W, Worthington, J, Barton, A & BIRAC consortium 2010, 'Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease' Arthritis Research & Therapy, vol. 12, no. 5, R175. https://doi.org/10.1186/ar3139
Eyre, Stephen ; Hinks, Anne ; Bowes, John ; Flynn, Edward ; Martin, Paul ; Wilson, Anthony G. ; Morgan, Ann W. ; Emery, Paul ; Steer, Sophia ; Hocking, Lynne J ; Reid, David M. ; Harrison, Pille ; Wordsworth, Paul ; Thomson, Wendy ; Worthington, Jane ; Barton, Anne ; BIRAC consortium. / Overlapping genetic susceptibility variants between three autoimmune disorders : rheumatoid arthritis, type 1 diabetes and coeliac disease. In: Arthritis Research & Therapy. 2010 ; Vol. 12, No. 5.
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T1 - Overlapping genetic susceptibility variants between three autoimmune disorders

T2 - rheumatoid arthritis, type 1 diabetes and coeliac disease

AU - Eyre, Stephen

AU - Hinks, Anne

AU - Bowes, John

AU - Flynn, Edward

AU - Martin, Paul

AU - Wilson, Anthony G.

AU - Morgan, Ann W.

AU - Emery, Paul

AU - Steer, Sophia

AU - Hocking, Lynne J

AU - Reid, David M.

AU - Harrison, Pille

AU - Wordsworth, Paul

AU - Thomson, Wendy

AU - Worthington, Jane

AU - Barton, Anne

AU - BIRAC consortium

PY - 2010/9/20

Y1 - 2010/9/20

N2 - Introduction: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD).Methods: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant.Results: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 x 10(-4)). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold.Conclusions: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation.

AB - Introduction: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD).Methods: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant.Results: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 x 10(-4)). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold.Conclusions: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation.

KW - juvenile idiopathic arthritis

KW - genome-wide association

KW - risk

KW - loci

KW - classification

KW - expression

KW - common

U2 - 10.1186/ar3139

DO - 10.1186/ar3139

M3 - Article

VL - 12

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 5

M1 - R175

ER -