Inflammatory Bowel Disease and Risk of More than 1,500 Comorbidities: A Disease-wide Prediagnostic and Postdiagnostic Phenomic Association Study.

Introduction: Inflammatory bowel disease (IBD) is associated with various extraintestinal manifestations. We aimed to identify comorbidities in IBD and the timing of their development to provide potentially useful insight into the associations with IBD.

Methods: We conducted a population and disease-wide phenomic association study in IBD, using >6 million International Classification of Diseases, Tenth Revision coded healthcare contacts from 10 years before and up-to 17 years after IBD diagnosis to investigate associations with 1,583 comorbidities. To explore diseases with potential etiological significance, we compared association in the prediagnostic and the postdiagnostic periods. We corrected also for multiple-testing. These estimates were validated with publicly available data from Finland.

Results: We identified 312 significant associations with 125 appearing before diagnosis. Risk of extraintestinal manifestations was increased up to 10 years before IBD diagnosis, such as psoriasis (OR CD : 2.58 95% confidence interval: [2.00-3.31]; OR UC : 1.54 [1.26-1.88]) and reactive arthropathies (OR CD : 2.07 [1.42-2.96]; OR UC : 1.42 [1.08-1.84]). Risk of cardiometabolic and neuropsychological disorders was increased both prediagnostically and postdiagnostically. Potential treatment sequelae, such as osteoporosis (HR CD : 2.56 [2.30-2.86]; HR UC : 1.92 [1.79-2.07]) were primarily seen postdiagnostically. In only 15.7% (44/281) and 11.4% (35/301) of comorbidities in Crohn's disease and ulcerative colitis, respectively, did we observe heterogeneity between Denmark and Finland.

Discussion: Findings demonstrate that IBD is a multisystemic disease, particularly manifesting with metabolic, immune, and neuropsychological disorders, up to 10 years before diagnosis. We find evidence for the generality of these findings with an international comparison. Diseases of etiological interest warrant further investigation.