Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

E. A.M. Festen; P. Goyette; R. Scott; V. Annese; A. Zhernakova; J. Lian; C. Lefèbvre; S. R. Brant; J. H. Cho; M. S. Silverberg; K. D. Taylor; D. J. De Jong; P. C. Stokkers; D. Mcgovern; O. Palmieri; J. P. Achkar; R. J. Xavier; M. J. Daly; R. H. Duerr; C. Wijmenga; R. K. Weersma; J. D. Rioux

doi:10.1136/gut.2008.166918

Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

E. A.M. Festen, P. Goyette, R. Scott, V. Annese, A. Zhernakova, J. Lian, C. Lefèbvre, S. R. Brant, J. H. Cho, M. S. Silverberg, K. D. Taylor, D. J. De Jong, P. C. Stokkers, D. Mcgovern, O. Palmieri, J. P. Achkar, R. J. Xavier, M. J. Daly, R. H. Duerr, C. WijmengaR. K. Weersma, J. D. Rioux

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

117 Scopus citations

Abstract

Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. Methods: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35×10^-10, rs13119723 p = 8.60×10^-8, rs6840978 p = 3.07×10^-8, rs6822844 p = 2.77×10 ^-9). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86×10^-5). Conclusions: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

Original language	English (US)
Pages (from-to)	799-804
Number of pages	6
Journal	Gut
Volume	58
Issue number	6
DOIs	https://doi.org/10.1136/gut.2008.166918
State	Published - Jun 2009
Externally published	Yes

ASJC Scopus subject areas

Gastroenterology

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10.1136/gut.2008.166918

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Festen, E. A. M., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefèbvre, C., Brant, S. R., Cho, J. H., Silverberg, M. S., Taylor, K. D., De Jong, D. J., Stokkers, P. C., Mcgovern, D., Palmieri, O., Achkar, J. P., Xavier, R. J., Daly, M. J., Duerr, R. H., ... Rioux, J. D. (2009). Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis. Gut, 58(6), 799-804. https://doi.org/10.1136/gut.2008.166918

Festen, EAM, Goyette, P, Scott, R, Annese, V, Zhernakova, A, Lian, J, Lefèbvre, C, Brant, SR, Cho, JH, Silverberg, MS, Taylor, KD, De Jong, DJ, Stokkers, PC, Mcgovern, D, Palmieri, O, Achkar, JP, Xavier, RJ, Daly, MJ, Duerr, RH, Wijmenga, C, Weersma, RK & Rioux, JD 2009, 'Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis', Gut, vol. 58, no. 6, pp. 799-804. https://doi.org/10.1136/gut.2008.166918

@article{413fede23da044b79e456ea041866239,

title = "Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis",

abstract = "Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. Methods: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35×10-10, rs13119723 p = 8.60×10-8, rs6840978 p = 3.07×10-8, rs6822844 p = 2.77×10 -9). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86×10-5). Conclusions: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.",

author = "Festen, {E. A.M.} and P. Goyette and R. Scott and V. Annese and A. Zhernakova and J. Lian and C. Lef{\`e}bvre and Brant, {S. R.} and Cho, {J. H.} and Silverberg, {M. S.} and Taylor, {K. D.} and {De Jong}, {D. J.} and Stokkers, {P. C.} and D. Mcgovern and O. Palmieri and Achkar, {J. P.} and Xavier, {R. J.} and Daly, {M. J.} and Duerr, {R. H.} and C. Wijmenga and Weersma, {R. K.} and Rioux, {J. D.}",

year = "2009",

month = jun,

doi = "10.1136/gut.2008.166918",

language = "English (US)",

volume = "58",

pages = "799--804",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "6",

}

TY - JOUR

T1 - Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

AU - Festen, E. A.M.

AU - Goyette, P.

AU - Scott, R.

AU - Annese, V.

AU - Zhernakova, A.

AU - Lian, J.

AU - Lefèbvre, C.

AU - Brant, S. R.

AU - Cho, J. H.

AU - Silverberg, M. S.

AU - Taylor, K. D.

AU - De Jong, D. J.

AU - Stokkers, P. C.

AU - Mcgovern, D.

AU - Palmieri, O.

AU - Achkar, J. P.

AU - Xavier, R. J.

AU - Daly, M. J.

AU - Duerr, R. H.

AU - Wijmenga, C.

AU - Weersma, R. K.

AU - Rioux, J. D.

PY - 2009/6

Y1 - 2009/6

N2 - Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. Methods: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35×10-10, rs13119723 p = 8.60×10-8, rs6840978 p = 3.07×10-8, rs6822844 p = 2.77×10 -9). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86×10-5). Conclusions: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

AB - Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. Methods: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35×10-10, rs13119723 p = 8.60×10-8, rs6840978 p = 3.07×10-8, rs6822844 p = 2.77×10 -9). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86×10-5). Conclusions: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

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Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

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