Mendelian Disease Associations Reveal Novel Insights into Inflammatory BowelDisease

Han L1, Maciejewski M2, Brockel C3, Afzelius L2, Altman RB1,4,5. Inflamm Bowel Dis. 2018 Feb 15;24(3):471-481. doi: 10.1093/ibd/izx087.

Author information

1 Biomedical Informatics Training Program, Stanford University, Stanford, CA.

2 Inflammation & Immunology, Pfizer Inc., Cambridge, MA.

3 Hill's Pet Nutrition, Topeka KS.

4 Department of Genetics, Stanford University, Stanford, CA.

5 Department of Bioengineering, Stanford University, Stanford, CA.


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.

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