Causal associations between inflammatory bowel disease and anxiety: A bidirectional Mendelian randomization study
Open accessAbstract
BACKGROUND Anxiety is common in patients with inflammatory bowel disease (IBD), including those with ulcerative colitis (UC) and Crohn’s disease (CD); however, the causal relationship between IBD and anxiety remains unknown. AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis. METHODS Single nucleotide polymorphisms retrieved from genome-wide association studies (GWAS) of the European population were identified as genetic instrument variants. GWAS statistics for individuals with UC (6968 patients and 20464 controls; adults) and CD (5956 patients and 14927 controls; adults) were obtained from the International IBD Genetics Consortium. GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium (2565 patients and 14745 controls; adults) and FinnGen project (20992 patients and 197800 controls; adults), respectively. Inverse-variance weighted was applied to assess the causal relationship, and the results were strengthened by heterogeneity, pleiotropy and leave-one-out analyses. RESULTS Genetic susceptibility to UC was associated with an increased risk of anxiety [odds ratio: 1.071 (95% confidence interval: 1.009-1.135), P = 0.023], while genetic susceptibility to CD was not associated with anxiety. Genetic susceptibility to anxiety was not associated with UC or CD. No heterogeneity or pleiotropy was observed, and the leave-one-out analysis excluded the potential influence of a particular variant. CONCLUSION This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.
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He et al.'s bidirectional Mendelian randomization study found a genetic link between ulcerative colitis and anxiety but not Crohn's disease.
“This study reveals a genetic link between UC and anxiety, diverging from prior research associating higher anxiety with Crohn’s disease.”
From Evaluating genetic insights into ulcerative colitis and anxiety: Limitations and future directions (2024) · cites this paper as [1]
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Bowden, J., Davey Smith, G., Haycock, P. C., & Burgess, S. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21965 · Cited by 8,922 · see citing works
Verbanck, M., Chen, C.-Y., Neale, B., & Do, R. (2018) · Nature Genetics · doi:10.1038/s41588-018-0099-7 · Cited by 8,591 · see citing works
Self-citationCryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Interpreting findings from Mendelian randomization using the MR-Egger method.
Burgess, S., & Thompson, S. G. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-017-0255-x · Cited by 4,571 · see citing works
Emdin, C. A., Khera, A. V., & Kathiresan, S. (2017) · JAMA · doi:10.1001/jama.2017.17219 · Cited by 3,637 · see citing works
Liu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T., et al. (2015) · Nature Genetics · doi:10.1038/ng.3359 · Cited by 2,603 · see citing works
Guidelines for performing Mendelian randomization investigations
Burgess, S., Smith, G. D., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Holmes, M. V., Minelli, C., Relton, C. L., et al. (2019) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15555.1 · Cited by 1,816 · see citing works
Guidelines for performing Mendelian randomization investigations
Burgess, S., Davey Smith, G., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Holmes, M. V., Minelli, C., Relton, C. L., et al. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15555.2 · Cited by 1,273 · see citing works
The microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999 · see citing works
Rogler, G., Singh, A. G., Kavanaugh, A., & Rubin, D. T. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.042 · Cited by 900 · see citing works
The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders
Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105840 · Cited by 857 · see citing works
Signaling inflammation across the gut-brain axis
Agirman, G., Yu, K. B., & Hsiao, E. Y. (2021) · Science · doi:10.1126/science.abi6087 · Cited by 846 · see citing works
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases
Quigley, E. M. M. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0802-6 · Cited by 804 · see citing works
Barberio, B., Zamani, M., Black, C. J., Savarino, E. V., & Ford, A. C. (2021) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00014-5 · Cited by 758 · see citing works
Guidelines for performing Mendelian randomization investigations: update for summer 2023
Burgess, S., Smith, G. D., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Kutalik, Z., Holmes, M. V., Minelli, C., et al. (2023) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15555.3 · Cited by 737 · see citing works
Psychiatric Genomics: An Update and an Agenda
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Børglum, A. D., Breen, G., Cichon, S., Edenberg, H. J., Faraone, S. V., Gelernter, J., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17030283 · Cited by 676 · see citing works
Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility
Spencer, N. J., & Hu, H. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0271-2 · Cited by 607 · see citing works
Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment
Bisgaard, T. H., Allin, K. H., Keefer, L., Ananthakrishnan, A. N., & Jess, T. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00634-6 · Cited by 572 · see citing works
Depression and anxiety in patients with Inflammatory Bowel Disease: a systematic review
Neuendorf, R., Harding, A., Stello, N., Hanes, D., & Wahbeh, H. (2016) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2016.06.001 · Cited by 561 · see citing works
Meta-analysis of genome-wide association studies of anxiety disorders
Otowa, T., Hek, K., Lee, M., Byrne, E. M., Mirza, S. S., Nivard, M. G., Bigdeli, T. B., Aggen, S. H., Adkins, D. E., Wolen, A. R., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.197 · Cited by 558 · see citing works
Newer Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease
Baumgart, D. C., & Berre, C. L. (2021) · New England Journal of Medicine · doi:10.1056/nejmra1907607 · Cited by 363 · see citing works
Gracie, D. J., Hamlin, P. J., & Ford, A. C. (2019) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(19)30089-5 · Cited by 358 · see citing works
Mitsialis, V., Wall, S. M., Liu, P., Ordovás-Montañés, J., Parmet, T., Vukovic, M., Spencer, D., Field, M., McCourt, C. C., Toothaker, J. M., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.04.074 · Cited by 354 · see citing works
Xu, Y., Sheng, H., Bao, Q., Wang, Y., Lu, J., & Ni, X. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.02.022 · Cited by 297 · see citing works
Increased burden of psychiatric disorders in inflammatory bowel disease
Bernstein, C. N., Hitchon, C. A., Walld, R., Bolton, J. M., Sareen, J., Walker, J. R., Graff, L. A., Patten, S. B., Singer, A., Lix, L. M., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy235 · Cited by 274 · see citing works
Kidney damage causally affects the brain cortical structure: A Mendelian randomization study
Chen, X., Kong, J., Pan, J., Huang, K., Zhou, W., Diao, X., Cai, J., Zheng, J., Yang, X., Xie, W., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103592 · Cited by 269 · see citing works
Frolkis, A. D., Vallerand, I. A., Shaheen, A.-A., Lowerison, M. W., Swain, M. G., Barnabe, C., Patten, S. B., & Kaplan, G. G. (2019) · Gut · doi:10.1136/gutjnl-2018-317182 · Cited by 228 · see citing works
Fairbrass, K. M., Lovatt, J., Barberio, B., Yuan, Y., Gracie, D. J., & Ford, A. C. (2022) · Gut · doi:10.1136/gutjnl-2021-325985 · Cited by 225 · see citing works
Immune-to-Brain Communication Pathways in Inflammation-Associated Sickness and Depression
D’Mello, C., & Swain, M. G. (2016) · Current topics in behavioral neurosciences · doi:10.1007/7854_2016_37 · Cited by 210 · see citing works
Disorders of the enteric nervous system — a holistic view
Niesler, B., Küerten, S., Demir, İ. E., & Schäfer, K. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00385-2 · Cited by 198 · see citing works
Borges, M. C., Haycock, P., Zheng, J., Hemani, G., Holmes, M. V., Smith, G. D., Hingorani, A. D., & Lawlor, D. A. (2022) · BMC Medicine · doi:10.1186/s12916-022-02399-w · Cited by 187 · see citing works
Rosoff, D. B., Smith, G. D., & Lohoff, F. W. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.3554 · Cited by 186 · see citing works
Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms
Ghasemi, M., Navidhamidi, M., Rezaei, F., Azizikia, A., & Mehranfard, N. (2021) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-021-00973-y · Cited by 167 · see citing works
Inflammatory Bowel Disease: Crohn’s disease and ulcerative colitis
Wehkamp, J., Goetz, M., Herrlinger, K. R., Steurer, W., & Stange, E. F. (2016) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2016.0072 · Cited by 162 · see citing works
Depression and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study
Luo, J. M., Xu, Z., Noordam, R., van Heemst, D., & Li‐Gao, R. (2021) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjab191 · Cited by 155 · see citing works
Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease
Marrie, R. A., Walld, R., Bolton, J. M., Sareen, J., Walker, J. R., Patten, S. B., Singer, A., Lix, L. M., Hitchon, C. A., El-Gabalawy, R., et al. (2019) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796017000579 · Cited by 144 · see citing works
Association Between Inflammatory Bowel Disease and Both Psoriasis and Psoriatic Arthritis
Freuer, D., Linseisen, J., & Meisinger, C. (2022) · JAMA Dermatology · doi:10.1001/jamadermatol.2022.3682 · Cited by 122 · see citing works
Butwicka, A., Olén, O., Larsson, H., Halfvarson, J., Almqvist, C., Lichtenstein, P., Serlachius, E., Frisén, L., & Ludvigsson, J. F. (2019) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2019.2662 · Cited by 117 · see citing works
Tang, M., Huang, H., Li, S., Zhou, M., Liu, Z., Huang, R., Liao, W., Xie, P., & Zhou, J. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0605-4 · Cited by 108 · see citing works
Haj-Mirzaian, A., Amiri, S., Amini-Khoei, H., Hosseini, M.-J., Haj-Mirzaian, A., Momeny, M., Rahimi-Balaei, M., & Dehpour, A. R. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.023 · Cited by 100 · see citing works
Depression and Anxiety Disorders in Patients With Inflammatory Bowel Disease
Hu, S., Chen, Y., Chen, Y., & Wang, C. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.714057 · Cited by 91 · see citing works
Ludvigsson, J. F., Olén, O., Larsson, H., Halfvarson, J., Almqvist, C., Lichtenstein, P., & Butwicka, A. (2021) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjab039 · Cited by 76 · see citing works
Baurecht, H., Welker, C., Baumeister, S., Weidinger, S., Meisinger, C., Leitzmann, M. F., & Emmert, H. (2021) · British Journal of Dermatology · doi:10.1111/bjd.20092 · Cited by 42 · see citing works
Vitali, R., Prioreschi, C., Lorenzo-Rebenaque, L., Colantoni, E., Giovannini, D., Frusciante, S., Diretto, G., Marco‐Jiménez, F., Mancuso, M., Casciati, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911495 · Cited by 39 · see citing works
Cooney, R., Tang, D., Barrett, K., & Russell, R. K. (2024) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izad169 · Cited by 39 · see citing works
Arp, L., Jansson, S., Wewer, V., & Burisch, J. (2022) · Journal of Crohn's and Colitis · doi:10.1093/ecco-jcc/jjac095 · Cited by 38 · see citing works
The Effects of Fatty Acids on Inflammatory Bowel Disease: A Two-Sample Mendelian Randomization Study
He, J., Luo, X., Xin, H., Lai, Q., Zhou, Y., & Bai, Y. (2022) · Nutrients · doi:10.3390/nu14142883 · Cited by 30 · see citing works
Self-citationIntercontinental Gut Microbiome Variances in IBD
Mayorga, L., Serrano-Gómez, G., Xie, Z., Borruel, N., & Manichanh, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810868 · Cited by 13 · see citing works
What can we do to tackle anxiety and depression in patients with inflammatory bowel disease?
Keefer, L. (2021) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00066-2 · Cited by 8 · see citing works
What is Mendelian randomization?
Burgess, S., & Thompson, S. G. (2015) · Chapman & Hall/CRC eBooks · doi:10.1201/b18084-7 · Cited by 1 · see citing works
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Kamp, K., Yang, P.-L., Tsai, C.-S., Zhang, X., Yoo, L., Altman, M. R., Heitkemper, M. M., Conley, S., Kane, S. V., & Winders, S. (2024) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izae279 · Cited by 8 · see citing works
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- Authors
- He, Y., Chen, C.-L., He, J., & Liu, S.-D.
- Affiliations
- Nanfang Hospital (CN)
- Guangdong Academy of Medical Sciences (CN)
- ORCID
- He, Jian
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2023-11-28
- Volume
- 29
- Issue
- 44
- Pages
- 5872-5881
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC10725559
- OpenAlex
- W4389055095
- Cited by
- 10
- References
- 50
- Citations by year
- 2025: 5 · 2024: 5
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Research Manitoba
- Crohn's and Colitis Canada
- Canadian Institutes of Health Research (135234_1, 333252)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- inflammatory bowel disease, anxiety, ulcerative colitis, Crohn's disease, bidirectional causality, genetic susceptibility, single nucleotide polymorphisms, anxiety screening, psychosocial comorbidity
- MeSH terms
- Adult, Anxiety, Colitis, Ulcerative, Crohn Disease, Humans, Inflammatory Bowel Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study, Mendelian Randomization Analysis
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