A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5

N J Prescott; S A Fisher; A Franke; J Hampe; C M Onnie; D Soars; R Bagnall; M M Mirza; J Sanderson; A Forbes; J C Mansfield; C M Lewis; S Schreiber; C G Mathew

doi:10.1053/j.gastro.2007.03.034

A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5

N J Prescott, S A Fisher, A Franke, J Hampe, C M Onnie, D Soars, R Bagnall, M M Mirza, J Sanderson, A Forbes, J C Mansfield, C M Lewis, S Schreiber, C G Mathew

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Abstract

Background & Aims: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. Methods: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. Results: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). Conclusions: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease

Original language	English
Pages (from-to)	1665 - 1671
Number of pages	7
Journal	Gastroenterology
Volume	132
Issue number	5
DOIs	https://doi.org/10.1053/j.gastro.2007.03.034
Publication status	Published - May 2007

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10.1053/j.gastro.2007.03.034

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Prescott, N. J., Fisher, S. A., Franke, A., Hampe, J., Onnie, C. M., Soars, D., Bagnall, R., Mirza, M. M., Sanderson, J., Forbes, A., Mansfield, J. C., Lewis, C. M., Schreiber, S., & Mathew, C. G. (2007). A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5. Gastroenterology, 132(5), 1665 - 1671. https://doi.org/10.1053/j.gastro.2007.03.034

@article{b67c23ddb4ad437294bfed5b008840c9,

title = "A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5",

abstract = "Background & Aims: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. Methods: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. Results: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). Conclusions: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease",

author = "Prescott, {N J} and Fisher, {S A} and A Franke and J Hampe and Onnie, {C M} and D Soars and R Bagnall and Mirza, {M M} and J Sanderson and A Forbes and Mansfield, {J C} and Lewis, {C M} and S Schreiber and Mathew, {C G}",

year = "2007",

month = may,

doi = "10.1053/j.gastro.2007.03.034",

language = "English",

volume = "132",

pages = "1665 -- 1671",

journal = "Gastroenterology",

issn = "1528-0012",

publisher = "WB Saunders",

number = "5",

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Prescott, NJ , Fisher, SA, Franke, A, Hampe, J, Onnie, CM, Soars, D, Bagnall, R, Mirza, MM, Sanderson, J, Forbes, A, Mansfield, JC, Lewis, CM, Schreiber, S & Mathew, CG 2007, 'A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5', Gastroenterology, vol. 132, no. 5, pp. 1665 - 1671. https://doi.org/10.1053/j.gastro.2007.03.034

TY - JOUR

T1 - A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5

AU - Prescott, N J

AU - Fisher, S A

AU - Franke, A

AU - Hampe, J

AU - Onnie, C M

AU - Soars, D

AU - Bagnall, R

AU - Mirza, M M

AU - Sanderson, J

AU - Forbes, A

AU - Mansfield, J C

AU - Lewis, C M

AU - Schreiber, S

AU - Mathew, C G

PY - 2007/5

Y1 - 2007/5

N2 - Background & Aims: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. Methods: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. Results: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). Conclusions: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease

AB - Background & Aims: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. Methods: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. Results: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). Conclusions: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease

U2 - 10.1053/j.gastro.2007.03.034

DO - 10.1053/j.gastro.2007.03.034

M3 - Article

SN - 1528-0012

VL - 132

SP - 1665

EP - 1671

JO - Gastroenterology

JF - Gastroenterology

IS - 5

ER -

A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and 1BD5

Abstract

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