Comorbidities, biomarkers and cause specific mortality in patients with irritable bowel syndrome: A phenome-wide association study

United European Gastroenterol J. 2023 May 7. doi: 10.1002/ueg2.12397. Online ahead of print.


Katharina Sophie Seeling 1Leonida Hehl 1Mara Sophie Vell 1Miriam Daphne Rendel 1Kate Townsend Creasy 2Christian Trautwein 1David Marc Anton Mehler 3 4Daniel Keszthelyi 5Kai Markus Schneider 1Carolin Victoria Schneider 1 6


Author information

1Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.

2Department of Biobehavioral Health Sciences, Perelman School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Aachen, Germany.

4Institute for Translational Psychiatry, University of Münster, Münster, Germany.

5Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands.

6The Institute for Translational Medicine and Therapeutics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.


Background: Irritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete.

Objective: To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality.

Methods: We analyzed data from the population-based cohort of the UK Biobank (UKB) with 493,974 participants, including self-reported physician-diagnosed (n = 20,603) and ICD-10 diagnosed (n = 7656) IBS patients, with a mean follow-up of 11 years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients.

Results: In PheWAS analyses, 260 PheCodes were significantly overrepresented in self-reported physician-diagnosed IBS patients, 633 in patients with ICD-10 diagnosed IBS (ICD-10-IBS), with 221 (40%) overlapping. In addition to gastrointestinal diseases, psychiatric, musculoskeletal, and endocrine/metabolic disorders represented the most strongly associated PheCodes in IBS patients. Self-reported physician-diagnosed IBS was not associated with increased overall mortality and the risk of death from cancer was decreased (hazard ratio [HR] = 0.78 [95% CI = 0.7-0.9]). Lastly, we evaluated changes in serum metabolites in IBS patients and identified glycoprotein acetyls (GlycA) as a potential biomarker in IBS. One standard deviation increase in GlycA raised the risk of self-reported IBS/ICD-10 coded by 9%-20% (odds ratio [OR] = 1.09 [95% CI = 1.1-1.1]/OR = 1.20 [95% CI = 1.1-1.3]) and the risk of overall mortality in ICD-10-IBS patients by 28% (HR = 1.28 [95% CI = 1.1-1.5]).

Conclusion: Our large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients.

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