Evidence map›Paper›PMID 18521914›Full record

ArticleInflammatory bowel diseases2008

Contributions of IBD5, IL23R, ATG16L1, and NOD2 to Crohn's disease risk in a population-based case-control study: evidence of gene-gene interactions.

Toshihiko Okazaki, Ming-Hsi Wang, Patricia Rawsthorne, Michael Sargent, Lisa Wu Datta, Yin Yao Shugart, Charles N Bernstein, Steven R Brant

Erratum issued Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammatory bowel diseases, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03262649 (Manitoba Inflammatory Bowel Disease Cohort Study), which is not on this map. Cited by 47 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 12 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03262649 completednot on this map

Manitoba Inflammatory Bowel Disease Cohort Study

TypeobservationalSponsorUniversity of ManitobaRan2002 to 2016Enrolled388ConditionsInflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 12 syntheses or guidelines pooled it, 76 citations in OpenAlex.

  1. Pooled it
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  3. Association between ATG16L1 gene polymorphism and the risk of Crohn's disease.The Journal of international medical research · 2017
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  8. Interleukin-23 receptor genetic polymorphisms and Crohn's disease susceptibility: a meta-analysis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2010
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Toshihiko OkazakiHarvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Ming-Hsi Wang
Patricia Rawsthorne
Michael Sargent
Lisa Wu Datta
Yin Yao Shugart
Charles N Bernstein
Steven R Brant
Johns Hopkins Medicine · USUniversity of Manitoba · CAJohns Hopkins University · US

Funding

Crohn's Disease Gene Mapping of Chromosome 16R01DK058189 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BRANT, STEVEN R · 2001 to 2005
$1.9M
NIDDK NIH HHS R01 DK058189NIDDK NIH HHS R01DK58189
6 · The paper itself

Abstract

backgroundIBD5, IL23R, and ATG16L1 genetic variations are established Crohn's disease (CD) risks alleles. We evaluated these in a population-based case-control study within a cohort to determine their penetrance, population attributable risk, independence, and relationship to other established CD risk factors, including NOD2.

methodsDNA from 213 CD, 118 [corrected] ulcerative colitis, and 315 [corrected] healthy control subjects from the population based University of Manitoba IBD Research Registry were genotyped for IBD5 and IL23R single-nucleotide polymorphisms (SNPs),and for the Thr 300Ala ATG16L1 SNP. Univariate and multivariate analyses were performed for these and nongenetic risk factors.We introduce multidimensionality reduction (MDR) to explore gene– gene interactions.

resultsATG16L1, IBD5, and IL23R SNPs were significantly associated with CD. Multivariate analysis showed independent CD association for carriers of ATG16L1 (odds ratio [OR] = 1.8, 95% confidence interval [CI] 1.09-3.24), IBD5-IGR2230 (OR = 2.16, 95% CI 1.30-3.59), and IL23R-rs10889677 (OR = 2.13, 95% CI 1.39-3.28) while retaining association for NOD2 mutation carriers (OR = 4.45, 95% CI 2.68-7.38), IBD family history (OR = 2.75, 95% CI 1.42-5.31), tobacco (OR = 2.06, 95% CI 1.35-3.14), and Jewish ethnicity (OR = 20.1, 95% CI 2.16-186.8). IL23R minor variants for Arg381Gln and Intron 6 rs7517848 showed independent, CD protection and 3' untranslated variant rs108896778 showed risk. MDR analysis suggested an interaction between IBD5, ATG16L1, and IL23R risk alleles. Penetrance values for ATG16L1 and IBD5 were 0.27% for heterozygotes, and 0.35% and 0.44%, respectively, for homozygotes. IL23R rs108896778 penetrance was 0.37%.

conclusionsA population-based analysis of CD risk factors is useful for characterizing the epidemiology of multiple CD genetic and nongenetic risk factors. Gene-gene interactions are likely, but require further evaluation in large population-based cohorts.

Indexed as

Polymorphism, GeneticAdolescentAdultCase-Control StudiesCohort StudiesColitis, UlcerativeCrohn DiseaseFemaleGene Expression RegulationGene FrequencyGenetic Predisposition to DiseaseGenetics, PopulationHaplotypesHumansIncidenceLogistic ModelsIL23R protein, humanNod2 Signaling Adaptor ProteinReceptors, Interleukin

Identifiers

PMID18521914
PMCPMC3336049
OpenAlexW1994499776

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.