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

Abstract

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. To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality. 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 11years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients. 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]). Our large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients.