After the Infection: A Survey of Pathogens
and Non-communicable Human Disease

Michael Lape^{1, 3, 4}, Daniel Schnell³, Sreeja Parameswaran^{4, 6}, Nathan Salomonis^{1, 2, 3}, Lisa J. Martin^{2, 6}, Brett M. Harnett¹, Leah C. Kottyan^{2, 4, 6, *}, Matthew T. Weirauch^{2, 3, 4, 5, 6, *}

¹Department of Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; ²Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; ³Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; ⁴Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; ⁵Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; ⁶Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; ^*Co-corresponding authors: Leah.Kottyan@cchmc.org; Matthew.Weirauch@cchmc.org

Abstract

There are many well-established relationships between pathogens and human disease, but far fewer when focusing on non-communicable diseases (NCDs). We leverage data from The UK Biobank and TriNetX to perform a systematic survey across 20 pathogens and 426 diseases, focused primarily on NCDs. To this end, we assess association between disease status and infection history proxies. We identify 206 pathogen-disease pairs that replicated in both cohorts. We replicated established relationships to validate our method, including Helicobacter pylori with several gastroenterological diseases, and connections between Epstein-Barr virus with multiple sclerosis and lupus. Our approach identified evidence of association for 15 of the pathogens and 96 distinct diseases, including a strong link between human cytomegalovirus (CMV) and ulcerative colitis (UC). We validate this connection through two orthogonal analyses, revealing increased CMV gene expression in UC patients and enrichment for UC genetic risk signal near human genes that have altered expression upon CMV infection. Collectively, these results form a foundation for future investigations into mechanistic roles played by pathogens in disease.

How to cite

Please cite this article as: Lape et al., After the Infection: A Survey of Pathogens and Non-communicable Human Disease, medRxiv (2023), https://www.medrxiv.org/content/10.1101/2023.09.14.23295428v1

Feedback

Have feedback on how we can make this resource better? Let us know.