Background:

Monogenic diseases have been shown to contribute to complex disease risk and may hold new insights into the underlying biological mechanism of Inflammatory Bowel Disease (IBD).

Methods:

We analyzed Mendelian disease associations with IBD using over 55 million patients from the Optum's deidentified electronic health records dataset database. Using the significant Mendelian diseases, we performed pathway enrichment analysis and constructed a model using gene expression datasets to differentiate Crohn's disease (CD), ulcerative colitis (UC), and healthy patient samples.

Results:

We found 50 Mendelian diseases were significantly associated with IBD, with 40 being significantly associated with both CD and UC. Our results for CD replicated those from previous studies. Pathways that were enriched consisted of mainly immune and metabolic processes with a focus on tolerance and oxidative stress. Our 3-way classifier for UC, CD, and healthy samples yielded an accuracy of 72%.

Conclusions:

Mendelian diseases that are significantly associated with IBD may reveal novel insights into the genetic architecture of IBD.