Association of ticagrelor with risk of infection：a two-sample Mendelian randomization study based on the GWAS database
- VernacularTitle:替格瑞洛与感染风险的关联：一项基于GWAS数据库的两样本孟德尔随机化研究
- Author:
Guifeng XU
1
,
2
;
Yonglin WU
2
,
3
;
Gongjie GUO
1
,
2
;
Junhong HUANG
4
;
Zhipeng XIE
1
,
2
;
Wenwei LUO
2
;
Shilong ZHONG
2
,
5
;
Weihua LAI
1
Author Information
1. School of Medicine，South China University of Technology，Guangzhou 510006，China
2. Dept. of Pharmacy，Guangdong Provincial People’s Hospital/Guangdong Academy of Medical Sciences，Southern Medical University，Guangzhou 510080，China
3. College of Pharmacy，Southern Medical University，Guangzhou 510515，China
4. School of Biology and Biological Engineering，South China University of Technology，Guangzhou 510006，China
5. Key Laboratory of Coronary Heart Disease Prevention and Treatment，Guangdong Provincial People’s Hospital/Guangdong Academy of Medical Sciences，Southern Medical University，Guangzhou 510080，China
- Publication Type:Journal Article
- Keywords:
ticagrelor;
infection;
Mendelian randomization;
genome-wide association analysis;
causal inference;
sepsis
- From:
China Pharmacy
2023;34(7):859-862
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae，acute upper respiratory infection and sepsis were furtheranalyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415） pleiotropy tests. RESULTS The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris （P＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），P＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98）， P＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （P＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （P＞0.05）. CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.
