基于双向孟德尔随机化研究循环免疫细胞与冠心病风险之间的因果关系

Causal Relationship Between Circulating Immune Cells and the Risk of Coronary Heart Disease:A Bidirectional Mendelian Randomization Based Study

目的通过孟德尔随机化分析(mendelian randomization,MR)探究免疫细胞与冠心病(coronary heart disease,CHD)之间潜在的因果关系。方法基于公开的全基因组关联分析(genome wide association study,GWAS)数据,利用孟德尔随机化分析探究731种免疫表型与CHD之间的关联。采用逆方差加权法作为评估因果效应的主要分析方法,并使用其他方法对逆方差加权法进行进一步的验证,同时进行了水平多效性检验、异质性检验和逐个剔除敏感性检验等敏感性分析。结果Bonferroni校正后,B细胞绝对计数与CHD风险增加有关(OR=1.064,95%CI:1.032~1.096,P<0.01),敏感性分析验证了结果稳定性,反向MR分析尚未发现CHD对免疫细胞有因果效应。其它免疫细胞特性对CHD的影响没有统计学意义,但具有未经调整的低P值。结论本研究通过遗传学手段证明了B细胞绝对计数与CHD之间的密切联系。这一发现为未来临床诊断及治疗CHD提供了新的依据。

Objective The immune response plays a crucial role in the progression of coronary heart disease(CHD).But the specific immune cells that may be causally related to CHD are still not fully understood.This study aimed to investigate the potential causal relationship between immune cells and CHD by using Mendelian randomization(MR)studies.Methods This study utilized publicly available Genome Wide Association Study(GWAS)data to analyze 731 immune traits in relation to CHD through MR analysis.The primary analytical method employed was the inverse variance weighting method to evaluate effects,with additional methods employed to corroborate the findings.Sensitivity analyses,including horizontal pleiotropy test,heterogeneity test,and leave-one-out methods were also carried out.Results Following Bonferroni correction,a significant correlation was found between B cell absolute count(OR=1.064,95%CI:1.032—1.096,P<0.01)and an increased risk of CHD.Sensitivity analysis was performed to confirm the reliability of these results.The inverse MR analysis suggested that there was no causal relationship between CHD and immune cells.Although other immune cell traits did not show a significant impact on CHD,they did exhibit low unadjusted P values.Conclusion This study highlighted the strong association between B cells and CHD at a genomic level,providing valuable insights for future clinical diagnosis and treatment.