BACKGROUND: We conducted a Mendelian randomization (MR) study to elucidate the anti-infective effects of ticagrelor. METHODS: Single-nucleotide polymorphisms (SNPs) associated with serum levels of ticagrelor or its major metabolite AR-C124910XX (ARC) in the Platelet Inhibition and Patient Outcomes trial were selected as genetic proxies for ticagrelor exposure. Positive control analyses indicated that genetically surrogated serum ticagrelor levels (6 SNPs) but not ARC levels (2 SNPs) were significantly associated with lower risks of coronary heart disease. Therefore, the 6 SNPs were used as genetic instruments for ticagrelor exposure, and the genome-wide association study data for 5 infection outcomes were derived from the UK Biobank and FinnGen consortium. RESULTS: The 2-sample MR analyses based on inverse variance-weighted methods indicated that genetic liability to ticagrelor exposure could reduce the risk of bacterial pneumonia (odds ratio, 0.82
95% CI, .71-.95
P = 8.75E-03) and sepsis (odds ratio, 0.83
95% CI, .73-.94
P = 3.69E-03)
however, no causal relationship was detected between ticagrelor exposure and upper respiratory infection, pneumonia, and urinary tract infection. Extensive sensitivity analyses corroborated these findings. CONCLUSIONS: Our MR study provides further evidence for the preventive effects of ticagrelor on bacterial pneumonia and sepsis.