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

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

Abstract

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.