Skip navigation
Skip navigation

ATG16L1T300A shows strong associations with disease subgroups in a large Ausralian IBD populaton: further support for significant disease heterogeneity

Fowler, Elizabeth V; Doecke, James; Simms, Lisa A; Zhao, Zhen; Webb, Penelope M; Hayward, Nicholas K; Whiteman, David C; Florin, Timothy H.J.; Montgomery, Grant W; Cavanaugh, Juleen; Radford-Smith, Graham

Description

OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are the two most common forms of inflammatory bowel disease (IBD), representing a significant health-care burden. A variant in the autophagy gene ATG16L1 (T300A) has been newly identified as a CD susceptibility locus by genome-wide association. Our aim was to assess the contribution of T300A in determining disease susceptibility and phenotype in two independent Australian IBD cohorts and explore the relationship between T300A and...[Show more]

dc.contributor.authorFowler, Elizabeth V
dc.contributor.authorDoecke, James
dc.contributor.authorSimms, Lisa A
dc.contributor.authorZhao, Zhen
dc.contributor.authorWebb, Penelope M
dc.contributor.authorHayward, Nicholas K
dc.contributor.authorWhiteman, David C
dc.contributor.authorFlorin, Timothy H.J.
dc.contributor.authorMontgomery, Grant W
dc.contributor.authorCavanaugh, Juleen
dc.contributor.authorRadford-Smith, Graham
dc.date.accessioned2015-12-10T22:59:45Z
dc.identifier.issn0002-9270
dc.identifier.urihttp://hdl.handle.net/1885/61235
dc.description.abstractOBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are the two most common forms of inflammatory bowel disease (IBD), representing a significant health-care burden. A variant in the autophagy gene ATG16L1 (T300A) has been newly identified as a CD susceptibility locus by genome-wide association. Our aim was to assess the contribution of T300A in determining disease susceptibility and phenotype in two independent Australian IBD cohorts and explore the relationship between T300A and known CD risk factors (NOD2 [nucleotide-binding oligomerization domain containing 2] status and smoking). METHODS: In total, 669 CD and 543 UC cases, and 1,244 controls (study 1), 154 CD cases and 420 controls (study 2), and 702 unaffected parents from both groups were genotyped. We conducted case-control and family association analyses, and investigated relationships between T300A and disease subgroups and between NOD2 status and cigarette smoking (CD only). RESULTS: The strong association between CD and T300A was confirmed (P < 0.001), with a two-fold increase in disease risk associated with the GG genotype (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.49-2.58), while ileal CD risk was almost three-fold (OR 2.73, CI 1.87-4.0). ATG16L1 and NOD2 were found to contribute independently to CD risk. A greater than seven-fold increased CD risk was observed for current smokers with a GG genotype (vs nonsmoking AA genotype; P < 0.001, OR 7.65, CI 4.21-13.91). A significant inverse association was found between T300A and UC (P = 0.002). This was strongest for patients with extensive, severe disease. CONCLUSIONS: We confirm the strong association between T300A and CD, specifically ileal subphenotype, and also report the first strong association of this variant with UC.
dc.publisherElsevier
dc.sourceAmerican Journal of Gastroenterology
dc.subjectKeywords: caspase recruitment domain protein 15; article; atg16l1 gene; Australia; autophagy; cigarette smoking; controlled study; gene; gene locus; genetic association; genetic heterogeneity; genetic susceptibility; genotype; human; human tissue; irritable colon;
dc.titleATG16L1T300A shows strong associations with disease subgroups in a large Ausralian IBD populaton: further support for significant disease heterogeneity
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume103
dc.date.issued2008
local.identifier.absfor060404 - Epigenetics (incl. Genome Methylation and Epigenomics)
local.identifier.ariespublicationu9204316xPUB596
local.type.statusPublished Version
local.contributor.affiliationFowler, Elizabeth V, Queensland Institute of Medical Research
local.contributor.affiliationDoecke, James, Queensland Institute of Medical Research
local.contributor.affiliationSimms, Lisa A, Royal Brisbane Women's Research Foundation
local.contributor.affiliationZhao, Zhen, Queensland Institute of Medical Research
local.contributor.affiliationWebb, Penelope M, Queensland Institute of Medical Research
local.contributor.affiliationHayward, Nicholas K, Queensland Institute of Medical Research
local.contributor.affiliationWhiteman, David C, Queensland Institute of Medical Research
local.contributor.affiliationFlorin, Timothy H.J., Mater Medical Research Institute
local.contributor.affiliationMontgomery, Grant W, Queensland Institute of Medical Research
local.contributor.affiliationCavanaugh, Juleen, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRadford-Smith, Graham, Royal Brisbane Hospital
local.description.embargo2037-12-31
local.bibliographicCitation.issue10
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage27
local.identifier.doi10.1111/j.1572-0241.2008.02023.x
dc.date.updated2015-12-10T08:15:56Z
local.identifier.scopusID2-s2.0-53149144667
local.identifier.thomsonID000260178400016
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Fowler_ATG16L1T300A_shows_strong_2008.pdf358.07 kBAdobe PDF    Request a copy


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator