Inflammatory bowel disease and risk of more than 1500 comorbidities: A disease-wide pre- and post-diagnostic phenomic association study

Abstract

Background and Aims:Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with various extra-intestinal manifestations. Identifying comorbidities in IBD and timing of their development provides valuable insight into mechanisms underlying IBD.Methods:We conducted a population- and disease-wide phenomic association study in IBD, using >6 million ICD-10 coded healthcare contacts from 10 years before and up-to 17 years after IBD diagnosis to investigate associations with 1583 comorbidities. To explore diseases with potential aetiological significance, we compared strength of association with co-morbidities in the pre-diagnostic with the post-diagnostic period. To correct for multiple testing, we adjust the significance threshold with the Bonferroni correction (p-value <7.90×10-6).Results:We identified 312 statistically significant associations with 125 of these appearing before diagnosis. Risk of immune-mediated diseases and extra-intestinal manifestations is increased up to 10 years prior to IBD diagnosis (e.g., enteropathic arthropathies: RRCD: 3.57, 95% CI: 2.65-4.78; RRUC: 1.8, 95% CI: 1.38-2.32). As with hepatic and pancreatic disorders (e.g., acute pancreatitis: RRCD: 1.83, 95% CI: 1.30-2.53; RRUC: 2.27, 95% CI: 1.84-2.79). Risk of cardiometabolic diseases and neuropsychological disorders was increased both pre- and post-diagnostically. Potential sequelae of treatment, such as osteoporosis (HRCD: 2.56, 95% CI: 2.30-2.86; HRUC: 1.92, 95% CI: 1.79-2.07) were primarily seen post-diagnostically. Infectious mononucleosis (RR: 1.87, 95% CI: 1.37-2.52) was significantly associated with the pre- compared to the post-diagnostic period for CD.Conclusion:Findings demonstrate that IBD is a multisystemic disease, particularly manifesting with metabolic, immune, and neuropsychological disorders, up-to 10 years prior to diagnosis. Diseases of aetiological interest identified warrant further investigation.