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. Lefebvre; 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. Lefebvre
, 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^*

^*Corresponding author for this work

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

129 Citations (Scopus)

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 = 1.35x10(-10), rs13119723 p = 8.60x10(-8), rs6840978 p = 3.07x10(-8), rs6822844 p = 2.77x10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86x10(-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
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
Publication status	Published - Jun-2009

Keywords

GENOME-WIDE ASSOCIATION
INFLAMMATORY-BOWEL-DISEASE
SYSTEMIC-LUPUS-ERYTHEMATOSUS
CELIAC-DISEASE
CROHNS-DISEASE
SUSCEPTIBILITY LOCI
BARRIER DEFECT
RISK VARIANTS
MYOSIN IXB
INTERLEUKIN-21

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Festen, E. A. M., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefebvre, 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

@article{f4260c7a0d7745cfa49285c71a60ed5c,

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 = 1.35x10(-10), rs13119723 p = 8.60x10(-8), rs6840978 p = 3.07x10(-8), rs6822844 p = 2.77x10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86x10(-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.",

keywords = "GENOME-WIDE ASSOCIATION, INFLAMMATORY-BOWEL-DISEASE, SYSTEMIC-LUPUS-ERYTHEMATOSUS, CELIAC-DISEASE, CROHNS-DISEASE, SUSCEPTIBILITY LOCI, BARRIER DEFECT, RISK VARIANTS, MYOSIN IXB, INTERLEUKIN-21",

author = "Festen, \{E. A. M.\} and P. Goyette and R. Scott and V. Annese and A. Zhernakova and J. Lian and C. Lefebvre 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 J-P Achkar 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",

volume = "58",

pages = "799--804",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "6",

}

Festen, EAM, Goyette, P, Scott, R, Annese, V, Zhernakova, A, Lian, J, Lefebvre, C, Brant, SR, Cho, JH, Silverberg, MS, Taylor, KD, de Jong, DJ, Stokkers, PC, Mcgovern, D, Palmieri, O, Achkar, J-P, 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

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 - Lefebvre, 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 = 1.35x10(-10), rs13119723 p = 8.60x10(-8), rs6840978 p = 3.07x10(-8), rs6822844 p = 2.77x10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86x10(-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 = 1.35x10(-10), rs13119723 p = 8.60x10(-8), rs6840978 p = 3.07x10(-8), rs6822844 p = 2.77x10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86x10(-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.

KW - GENOME-WIDE ASSOCIATION

KW - INFLAMMATORY-BOWEL-DISEASE

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - CELIAC-DISEASE

KW - CROHNS-DISEASE

KW - SUSCEPTIBILITY LOCI

KW - BARRIER DEFECT

KW - RISK VARIANTS

KW - MYOSIN IXB

KW - INTERLEUKIN-21

U2 - 10.1136/gut.2008.166918

DO - 10.1136/gut.2008.166918

M3 - Article

SN - 0017-5749

VL - 58

SP - 799

EP - 804

JO - Gut

JF - Gut

IS - 6

ER -

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

Abstract

Keywords

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