Interleukin-18 as a drug repositioning opportunity for inflammatory bowel disease: A Mendelian randomization study.

ABSTRACT: Support from human genetics increases the probability of success in drug development. However, few examples exist of successful genomically-driven drug repositioning. Given that a Mendelian form of severe enterocolitis is due to up-regulation of the interleukin-18 (IL18) signaling pathway, and pharmacologic inhibition of IL18 has been shown to reverse this enterocolitis, we undertook a Mendelian randomization study to test the causal effect of elevated IL18 levels on inflammatory bowel disease susceptibility (IBD) in 12,882 cases and 21,770 controls. Mendelian randomization is an established method to assess the role of biomarkers in disease etiology in a manner that minimizes confounding and prevents reverse causation. Using three SNPs that explained almost 7% of the variance in IL18 leve

SUBMITTER: Mokry LE 

PROVIDER: S-EPMC6599045 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature