Original Research Full Report: Basic and Translational—Alimentary Tract| Volume 160, ISSUE 3, P771-780.e4, February 01, 2021

Prevalence and Effect of Genetic Risk of Thromboembolic Disease in Inflammatory Bowel Disease

Published:October 21, 2020DOI:

      Background And Aims

      The largest cause of mortality in patients with inflammatory bowel disease (IBD) remains thromboembolic disease (TED). Recent reports have demonstrated that both monogenic and polygenic factors contribute to TED and 10% of healthy subjects are genetically at high risk for TED. Our aim was to utilize whole-exome sequencing and genome-wide genotyping to determine the proportion of IBD patients genetically at risk for TED and investigate the effect of genetic risk of TED in IBD.


      The TED polygenic risk score was calculated from genome-wide genotyping. Thrombophilia pathogenic variants were extracted from whole-exome sequencing. In total, 792 IBD patients had both whole-exome sequencing and genotyping data. We defined patients at genetically high risk for TED if they had a high TED polygenic risk score or carried at least 1 thrombophilia pathogenic variant.


      We identified 122 of 792 IBD patients (15.4%) as genetically high risk for TED. Among 715 of 792 subjects whose documented TED status were available, 63 of the 715 patients (8.8%) had TED events. Genetic TED risk was significantly associated with increased TED event (odds ratio, 2.5; P = .0036). In addition, we confirmed an additive effect of monogenic and polygenic risk on TED (P = .0048). Patients with high TED genetic risk more frequently had thrombosis at multiple sites (78% vs 42%, odds ratio, 3.96; P = .048).


      Genetic risk (both poly- and monogenic) was significantly associated with TED history. Our results suggest that genetic traits identify approximately 1 in 7 patients with IBD who will experience 2.5-fold or greater risk for TED.

      Graphical abstract


      Abbreviations used in this paper:

      CD (Crohn’s disease), IBD (inflammatory bowel disease), OR (odds ratio), PRS (polygenic risk score), QC (quality control), SNP (single nucleotide polymorphism), TED (thromboembolic disease), TPV (thrombophilia pathogenic variant), UC (ulcerative colitis), WES (whole-exome sequencing)
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