C反应蛋白与心脏传导障碍两样本孟德尔随机化研究
C-reactive protein and cardiac conduction disorders:a two-sample Mendelian randomization study
刘道申 1田文杰 2李晶3
作者信息
- 1. 北部战区总医院 心血管内科,辽宁 沈阳 110016;空军军医大学西京医院 心血管内科,陕西 西安 710032
- 2. 九六一一〇部队医院 心血管内科,宁夏 银川 750000
- 3. 北部战区总医院 心血管内科,辽宁 沈阳 110016
- 折叠
摘要
目的 探讨C反应蛋白(CRP)与心脏传导障碍的因果关联.方法 使用两样本孟德尔随机化分析方法,选择与血清CRP浓度相关的单核苷酸多态性(SNP)作为工具变量,在204 402 例欧洲血统个体的全基因组关联研究中进行分析.利用FinnGen数据库(第 2 版)的汇总数据,分别获得与 3 种心脏传导障碍[房室传导阻滞(AV-block)、左束支传导阻滞(LBBB)、右束支传导阻滞(RBBB)]相关的遗传变异.采用逆方差加权法进行主分析,然后分别应用敏感性分析、多效性检验和留一法评估结果的可靠性.结果 共50 个SNPs纳入为工具变量.逆方差加权分析显示,遗传预测的血清CRP浓度与心脏传导障碍之间无明显因果关联,结果分别为AV-block(比值比0.983,95%可信区间0.820～1.177,P=0.849)、LBBB(比值比1.201,95%可信区间0.911～1.583,P=0.194)、RBBB(比值比1.292,95%可信区间0.881～1.894,P=0.194).敏感性分析结果显示,CRP与AV-block、LBBB和RBBB均无显著相关性(P>0.05).多效性检验显示,CRP与AV-block、LBBB和RBBB均不存在异质性和多效性(P>0.05).留一法提示,移除单个SNP对结果无显著影响.结论 血清CRP浓度与心脏传导障碍不存在因果关联.
Abstract
Objective To investigate the causal relationship between C-reactive protein(CRP)and cardiac conduction disorders.Methods Single nucleotide polymorphism(SNP)associated with serum CRP concentration were selected as instrumental variables in a genome-wide association study of 204 402 individuals of European ancestry using two-sample mendelian randomization analysis.Ge-netic variants associated with three heart conduction disorders[atrioventricular block(AV-block),left bundle branch block(LBBB),and right bundle branch block]were obtained using pooled data from the FinnGen database(2nd edition).The inverse variance weigh-ting method was used for the main analysis,and then sensitivity analysis,pleiotropy test and remain-one method were used respectively to evaluate the reliability of the results.Results A total of 50 SNPs were included as instrumental variables.Inverse variance weighted analysis showed no significant causal association between genetically predicted serum CRP concentration and cardiac conduction disor-ders,and the results were AV-block(odds ratio 0.983,95%confidence interval 0.820 to 1.177,P=0.849),LBBB(odds ratio 1.201,95%confidence interval 0.911 to 1.583,P=0.194)and RBBB(odds ratio 1.292,95%confidence interval 0.881 to 1.894,P=0.194).Sensitivity analysis showed that CRP was not significantly correlated with atrioventricular block,left bundle branch block and right bundle branch block(P>0.05).Pleiotropy test showed no heterogeneity or pleiotropy between CRP and AV-block,BBB,BB(P>0.05).The remain-one method suggests that removing a single SNP has no significant effect on the results.Conclusion There is no causal relationship between CRP concentration and cardiac conduction disorder.
关键词
孟德尔随机化/C反应蛋白/心脏传导障碍/心律失常/因果关联Key words
Mendelian randomization/C-reactive protein/Cardiac conduction disorders/Arrhythmia/Causal association引用本文复制引用
基金项目
国家重点研发计划(2022YFC2503500)
国家重点研发计划(2022YFC2503504)
出版年
2024
NETL
NSTL
万方数据