Smoking Interacts With CHRNA5, a Nicotinic Acetylcholine Receptor Subunit Gene, to Influence the Risk of IBD-Related Surgery
Open accessAbstract
Background: Inflammatory bowel disease (IBD) is a chronic luminal disease with genetic and environmental factors affecting phenotype.This study evaluated the relationship between CHRNA5, a nicotinic receptor subunit gene, and smoking in predicting IBD-related surgery as well as the relationship between CHRNA5 and nicotine dependence.Methods: Participants completed a smoking questionnaire and were genotyped for CHRNA5 rs16969968.Demographic and clinical data were obtained from medical records.Wilcoxon, ANOVA, Chi square, and Fisher's exact tests were used for comparisons.Logistic regression was used to evaluate the effect of clinical and genetic predictors on surgery, stratified by disease subtype given paradoxical effects of smoking.Kaplan-Meier curves were used to examine the effect of smoking and genotype on time to surgery.(Significance: P < 0.05 for main effects; P < 0.2 for interaction terms) Results: 400 (65.8%) patients had Crohn's disease (CD) and 208 (34.2%) had ulcerative colitis (UC).298 (49%) underwent an IBD-related surgery.There was a trend towards significance between rs16969968 and smoking behavior (smoking status [P = 0.05], nicotine dependence [AA > AG > GG; P = 0.08]).Smoking and genotype were not independently associated with surgery in UC or CD.However, interaction between rs16969968 and smoking in predicting surgery was observed for both UC (OR = 2.72; P = 0.05) and CD (OR = 2.88; P = 0.1).CHRNA5 genotype, but not smoking, predicted time to surgery in patients with UC (P = 0.007) but not in patients with CD.The interaction between smoking and genotype was not significantly associated with time to surgery in UC or CD. Conclusions:The CHRNA5 rs16969968 A variant interacts with smoking to influence IBD-related surgery.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CHRNA5 has been linked in several studies to smoking and various smoking risk factors.
“CHRNA5 has been linked in several studies to smoking and various smoking risk factors [53–57].”
From Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes (2022) · cites this paper as [54]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire
HEATHERTON, T. F., KOZLOWSKI, L. T., FRECKER, R. C., & FAGERSTROM, K. (1991) · British Journal of Addiction · doi:10.1111/j.1360-0443.1991.tb01879.x · Cited by 10,738 · see citing works
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228 · see citing works
Integrating common and rare genetic variation in diverse human populations
The International HapMap 3 Consortium (2010) · Nature · doi:10.1038/nature09298 · Cited by 3,026 · see citing works
Saccone, S. F., Hinrichs, A. L., Saccone, N. L., Chase, G. A., Konvicka, K., Madden, P. A. F., Breslau, N., Johnson, E. O., Hatsukami, D., Pomerleau, O., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl438 · Cited by 850 · see citing works
Statistical Analysis of Epidemiologic Data
Selvin, S. (2004) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195172805.001.0001 · Cited by 827 · see citing works
Clinical Course in Crohn’s Disease: Results of a Norwegian Population-Based Ten-Year Follow-Up Study
Solberg, I. C., Vatn, M. H., Høie, O., Stray, N., Sauar, J., Jahnsen, J., Moum, B. A., & Lygren, I. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.09.002 · Cited by 697 · see citing works
Variants in Nicotinic Receptors and Risk for Nicotine Dependence
Bierut, L. J., Stitzel, J. A., Wang, J. C., Hinrichs, A. L., Grucza, R. A., Xuei, X., Saccone, N. L., Saccone, S. F., Bertelsen, S., Fox, L., et al. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.07111711 · Cited by 648 · see citing works
Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis
Loddo, I., & Romano, C. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00551 · Cited by 451 · see citing works
Ramadas, A. V., Gunesh, S., Thomas, G. A. O., Williams, G. T., & Hawthorne, A. B. (2010) · Gut · doi:10.1136/gut.2009.202101 · Cited by 384 · see citing works
Surgery in a Population-Based Cohort of Crohn's Disease From Olmsted County, Minnesota (1970–2004)
Peyrin‐Biroulet, L., Harmsen, S. W., Tremaine, W. J., Zinsmeister, A. R., Sandborn, W. J., & Loftus, E. V. (2012) · The American Journal of Gastroenterology · doi:10.1038/ajg.2012.298 · Cited by 314 · see citing works
The vagal innervation of the gut and immune homeostasis
Matteoli, G., & Boeckxstaens, G. E. (2013) · Gut · doi:10.1136/gutjnl-2012-302550 · Cited by 276 · see citing works
Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice
Cosnes, J. (2004) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2003.12.003 · Cited by 244 · see citing works
To, N., Gracie, D. J., & Ford, A. C. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13511 · Cited by 189 · see citing works
Chen, L.-S., Baker, T. B., Piper, M. E., Breslau, N., Cannon, D. S., Doheny, K. F., Gogarten, S. M., Johnson, E. O., Saccone, N. L., Wang, J. C. C., et al. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11101545 · Cited by 143 · see citing works
Self-citationVon Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular Disease
Frankel, D. S., Meigs, J. B., Massaro, J. M., Wilson, P. W. F., O’Donnell, C. J., D’Agostino, R. B., & Tofler, G. H. (2008) · Circulation · doi:10.1161/circulationaha.108.792986 · Cited by 134 · see citing works
The intestinal cholinergic anti-inflammatory pathway
Goverse, G., Stakenborg, M., & Matteoli, G. (2016) · The Journal of Physiology · doi:10.1113/jp271537 · Cited by 109 · see citing works
Yadav, P., Ellinghaus, D., Rémy, G., Freitag‐Wolf, S., Cesaro, A., Degenhardt, F. C., Boucher, G., Delacre, M., Peyrin‐Biroulet, L., Pichavant, M., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.05.010 · Cited by 90 · see citing works
Fowler, E. V., Doecke, J. D., Simms, L. A., Zhao, Z., Webb, P. M., Hayward, N. K., Whiteman, D. C., Florin, T. H., Montgomery, G. W., Cavanaugh, J. A., et al. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.02023.x · Cited by 89 · see citing works
To, N., Ford, A. C., & Gracie, D. J. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13663 · Cited by 77 · see citing works
Pierik, M. J., Yang, H., Barmada, M. M., Cavanaugh, J. A., Annese, V., Brant, S. R., Cho, J. H., Duerr, R. H., Hugot, J., McGovern, D. P. B., et al. (2005) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200501000-00001 · Cited by 71 · see citing works
Li, W., Jiang, K., Yuan, W., Cui, W., & Li, M. D. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8997-x · Cited by 66 · see citing works
Kuenzig, M. E., Lee, S., Eksteen, B., Seow, C. H., Barnabe, C. C. M., Panaccione, R., & Kaplan, G. G. (2016) · BMC Gastroenterology · doi:10.1186/s12876-016-0555-8 · Cited by 65 · see citing works
Orr‐Urtreger, A., Kedmi, M., Rosner, S., Karmeli, F., & Rachmilewitz, D. (2005) · Neuroreport · doi:10.1097/00001756-200507130-00018 · Cited by 56 · see citing works
van der Heide, F., Nolte, I. M., Kleibeuker, J. H., Wijmenga, C., Dijkstra, G. D. H., & Weersma, R. K. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.659 · Cited by 47 · see citing works
Dissection of the Phenotypic and Genotypic Associations With Nicotinic Dependence
Chen, L., Baker, T. B., Grucza, R. A., Wang, J. C. C., Johnson, E. O., Breslau, N., Hatsukami, D. K., Smith, S. S., Saccone, N. L., Saccone, S. F., et al. (2011) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntr231 · Cited by 45 · see citing works
Self-citationGene–gene and gene–environment interactions in ulcerative colitis
Wang, M., Fiocchi, C., Zhu, X., Ripke, S., Kamboh, M. I., Rebert, N. A., Duerr, R. H., & Achkar, J. (2013) · Human Genetics · doi:10.1007/s00439-013-1395-z · Cited by 36 · see citing works
Helbig, K. L., Nothnagel, M., Hampe, J., Balschun, T. C., Nikolaus, S., Schreiber, S., Franke, A., & Nöthlings, U. (2012) · BMC Medical Genetics · doi:10.1186/1471-2350-13-14 · Cited by 29 · see citing works
CHRNA5 Variant Predicts Smoking Cessation in Patients With Acute Myocardial Infarction
Chen, L., Bach, R. G., Lenzini, P. A., Spertus, J. A., Bierut, L. J., & Cresci, S. (2014) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntu059 · Cited by 21 · see citing works
Self-citationSmoking behaviour modifies IL23r‐associated disease risk in patients with Crohn's disease
Doecke, J. D., Simms, L. A., Zhao, Z., Roberts, R. L., Fowler, E. V., Croft, A. R., Lin, A., Huang, N., Whiteman, D. C., Florin, T. H., et al. (2014) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12674 · Cited by 21 · see citing works
Xu, Z., Wang, G., Dong, Z., Li, T.-H., Cao, C., & Jin, Y. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.15.6685 · Cited by 19 · see citing works
Altarescu, G., Rachmilewitz, D., & Zevin, S. (2011) · PubMed · Cited by 11 · see citing works
Flagged first, then by citations
1 of the 33 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Guo, D., Li, X., Wang, J., Liu, X., Wang, Y., Huang, S., & Dang, N. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06583-z · Cited by 33 · see citing works
Dannemann, M., Milaneschi, Y., Yermakovich, D., Stiglbauer, V., Kariis, H. M., Krebs, K., Friese, M. A., Otte, C., Estonian Biobank Research Team, Esko, T., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02196-2 · Cited by 23 · see citing works
Bai, J., Bouwknegt, D. G., Weersma, R. K., Dijkstra, G. D. H., van der Sloot, K. W. J., & Festen, E. A. M. (2025) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjaf061 · Cited by 22 · see citing works
Wang, J., Li, X., Zhang, P., Yang, T., Liu, N., Qin, L., Ma, G., Li, X., Fan, H., Huang, S., et al. (2022) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2022.04.014 · Cited by 14 · see citing works
Global geoepidemiology of gastrointestinal surgery rates in Crohn’s disease
Weissman, S. I., Aziz, M., Bangolo, A., Nagesh, V. K., Aung, H., Mathew, M., Garcia, L. F. S., Chandar, S. A., Karamthoti, P., Bawa, H., et al. (2024) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v16.i6.1835 · Cited by 5 · see citing works
Dilly, R. D. S., Barretta, C., Matos, C. H. D., Piasecki, B. T., Scolaro, B. L., Malluta, É. F., Bobato, S. T., Specht, C. M., de Mello, M. K., Kimura, M. C., et al. (2019) · Journal of Coloproctology · doi:10.1016/j.jcol.2019.10.006 · Cited by 5 · see citing works
Zhang, Z., Ouyang, L., Sun, A., Pu, Z., Liu, Y., Peng, Y., & Li, X. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120539 · Cited by 1 · see citing works
Vastrad, B. M., & Vastrad, C. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.27.501664 · Cited by 1 · see citing works
Dang, N., Guo, D., Li, X., Wang, J., Liu, X., & Huang, S. (2023) · Research Square · doi:10.21203/rs.3.rs-3017107/v1
- Authors
- Cushing, K. C., Chiplunker, A., Li, A., Sung, Y. J., Geisman, T., Chen, L.-S., Cresci, S., & Gutierrez, A. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Cushing, Kelly C
- Venue
- Inflammatory Bowel Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-23
- Volume
- 24
- Issue
- 5
- Pages
- 1057-1064
- ISSN
- 1078-0998 (ISSN-L)
- 1536-4844
- PMC
- PMC5994591
- OpenAlex
- W4254402385
- Cited by
- 9
- References
- 33
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2019: 1
- FWCI
- 0.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Inflammatory Bowel Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- Funders
- National Institutes of Health (T32DK007130)
- Washington University Institute of Clinical and Translational Sciences (UL1TR000448)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- CHRNA5, nicotinic acetylcholine receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review