cover of episode Mendelian disease comorbidity as a resource for novel therapeutic targets

Mendelian disease comorbidity as a resource for novel therapeutic targets

2023/7/23
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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.23.550190v1?rss=1

Authors: Lalakgas, P. N., Melamed, R. D.

Abstract: Drugs targeting disease causal genes are more likely to succeed for that disease. But complex disease causal genes are not always clear. In contrast, Mendelian disease causal genes are well-known and druggable. In previous work, we examined 90 Mendelian and 65 complex diseases, finding 2,908 pairs of clinically associated (comorbid) diseases in which the Mendelian disease causal genes may have a pleiotropic effect on the complex disease. Here, we hypothesize that Mendelian disease causal genes can be potential therapeutic targets for the comorbid complex disease due to their pleiotropic effects. We match each complex disease to a set of Mendelian disease causal genes based on its comorbidity and suggest the drugs targeting these genes as potential drug candidates for the complex disease. We demonstrate that the candidate drugs are enriched among currently investigated or indicated drugs for the relevant complex diseases (OR=1.8, p=1.79e-21). We also present evidence that certain Mendelian diseases have a better potential for future drug discovery and drug repurposing applications. In conclusion, our findings suggest a novel way to take advantage of rich knowledge about Mendelian disease biology to improve treatments of common diseases.

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