ArticleBMC medical genetics2012
A case-only study of gene-environment interaction between genetic susceptibility variants in NOD2 and cigarette smoking in Crohn's disease aetiology.
Article in BMC medical genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Gene-Environment Interactions in Inflammatory Bowel Disease: A Systematic Review of Human Epidemiologic Studies.Journal of Crohn's & colitis · 2025Pooled it
- Pooled it
- Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.Gastroenterology · 2017Pooled it
- The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study.EBioMedicine · 2017Pooled it
- Nucleotide-binding oligomerization domain 2-independent colonization by Turicimonas muris induced by high-fat diet protects against dextran sodium sulfate-induced colitis.Clinical and experimental immunology · 2026Article
- Proanthocyanidins in immune-mediated inflammatory diseases: molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- The case-only design is a powerful approach to detect interactions but should be used with caution.BMC genomics · 2025Article
- NOD2 and Crohn's Disease Clinical Practice: From Epidemiology to Diagnosis and Therapy, Rewired.Inflammatory bowel diseases · 2025Review
- Identification of Potential Genes and Critical Pathways in Postoperative Recurrence of Crohn's Disease by Machine Learning And WGCNA Network Analysis.Current genomics · 2023Article
- The missing heritability in type 1 diabetes.Diabetes, obesity & metabolism · 2022Review
- Genome-wide association studies of structural birth defects: A review and commentary.Birth defects research · 2019Review
- From Genetics to Epigenetics, Roles of Epigenetics in Inflammatory Bowel Disease.Frontiers in genetics · 2019Review
- Smoking Interacts With CHRNA5, a Nicotinic Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD-Related Surgery.Inflammatory bowel diseases · 2018Article
- Interaction Between NOD2 and Smoking in the Pathogenesis of Crohn's Disease.EBioMedicine · 2017Review
- Application of computational methods in genetic study of inflammatory bowel disease.World journal of gastroenterology · 2016Review
- Deciphering Genome Environment Wide Interactions Using Exposed Subjects Only.Genetic epidemiology · 2015Article
- Role of Salmonella enterica exposure in Chilean Crohn's disease patients.World journal of gastroenterology · 2013Article
- Genetic and functional profiling of Crohn's disease: autophagy mechanism and susceptibility to infectious diseases.BioMed research international · 2013Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic variation in NOD2 and cigarette smoking are well-established risk factors for the development of Crohn's disease (CD). However, little is known about a potential interaction between these risk factors. We investigated gene-environment interactions between CD-associated NOD2 alleles and cigarette smoking in a large sample of patients with CD.
methodsThree previously reported CD-associated variants in NOD2 (R702W, G908R, 1007fs) were genotyped in 1636 patients with CD continuously recruited between 1995 and 2010 based on physician referral. Data on history of smoking behaviour was obtained for all participants through a written questionnaire. Using a case-only design, we performed logistic regression analyses to investigate statistical interactions between NOD2 risk alleles and smoking status.
resultsWe detected a significant negative interaction between carriership of at least one of the NOD2 risk alleles and history of ever having smoked (OR = 0.71; p = 0.005) as well as smoking at the time of CD diagnosis (OR = 0.68; p = 0.005). Subsequent separate analyses of the three variants revealed a significant negative interaction between the 1007fs variant and history of ever having smoked (OR = 0.64; p = 9 × 10-4) and smoking at the time of CD diagnosis (OR = 0.53; p = 7 × 10-5).
conclusionsThe observed significant negative gene-environment interaction suggests that the risk increase for CD conferred simultaneously by cigarette smoking and the 1007fs NOD2 polymorphism is smaller than expected and may point to a biological interaction. Our findings warrant further investigation in epidemiological and functional studies to elucidate pathophysiology as well as to aid in the development of recommendations for disease prevention.
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