孟德尔随机化
替卡格雷
医学
内科学
重症监护医学
遗传学
生物
遗传变异
急性冠脉综合征
基因型
心肌梗塞
基因
作者
Xia Meng,Qingmeng Wu,Ye Wang,Yongquan Peng,Cheng Qian
标识
DOI:10.1093/infdis/jiae177
摘要
Abstract Aims We conducted a Mendelian randomization (MR) study to elucidate the anti-infective effects of ticagrelor. Methods and results 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 (six SNPs) but not ARC levels (two SNPs) were significantly associated with lower risks of coronary heart disease. Therefore, the six SNPs were used as genetic instruments for ticagrelor exposure, and the genome-wide association study data for five infection outcomes were derived from the UK Biobank and FinnGen consortium. The two-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 [OR]: 0.82, 95% confidence interval [CI]: 0.71–0.95, P = 8.75E-03) and sepsis (OR: 0.83, 95% CI: 0.73–0.94, P = 3.69E-03); however, no causal relationship between ticagrelor exposure and upper respiratory infection, pneumonia, and urinary tract infection was detected. Extensive sensitivity analyses corroborated these findings. Conclusion Our MR study provides further evidence for the preventive effects of ticagrelor on bacterial pneumonia and sepsis.
科研通智能强力驱动
Strongly Powered by AbleSci AI