To explore the causal relationship between circulating immune cell phenotype and coronary heart disease based on two sample bidirectional Mendelian randomization analysis

Yuan Hang; Wang Daying

doi:10.3969/j.issn.1002-1949.2024.05.011

Abstract：Objective To explore whether there is a causal relationship between circulating immune cell phenotype and coronary heart disease.Methods The circulating immune cell phenotype was used as the exposure factor and coronary heart disease as the outcome event,single nucleotide polymorphisms(SNPs)closely related to the circulating immune cell phenotype and coronary heart disease were used as genetic instrumental variables.Two sample Mendelian randomization analysis was used to analyze the genome-wide association study(GWAS)data.GWAS data for the circulating immune cell phenotype and coronary heart disease were both sourced from the online GWAS database.The main analysis methods included inverse variance weighted(IVW),as well as simple mode,weighted median,weighted mode,and MR-Egger.The causal relationship between circulating immune cells and coronary heart disease was evaluated by odds ratio(OR)and 95%confidence interval(95%CI).Coronary heart disease was used as an exposure factor,and the above circulating immune cell phenotypes were used as the outcome event for reverse Mendelian randomization analysis in order to avoid reverse causality.Results This study screened 731 circulating immune cell phenotypes for Mendelian randomization analysis.The IVW method showed a causal relationship between 18 circulating immune cell phenotypes and coronary heart disease,and the results of other MR Egger methods were consistent with the direction of IVW.Among them,12 circulating immune cell phenotypes had a significant causal relationship with an increased risk of coronary heart disease,while 6 circulating immune cell phenotypes significantly reduced the risk of coronary heart disease.The MR-Egger regression results indicated that there was no genetic pleiotropy effect(P>0.05).Reverse analysis revealed a significant causal relationship of coronary heart disease with an increase in CD45 labeled natural killer T levels and a decrease in IgD-CD24-labeled B lymphocyte levels.Conclusions Multiple subsets of T and B cells have a significant impact on the incidence risk of coronary heart disease.In addition,coronary heart disease has a significant impact on the levels of CD45 labeled natural killer T cells and IgD-CD24-labeled B lymphocytes.This study focuses on the different effects of specific immune cells and the cellular responses they trigger,and emphasizes potential strategies for treating B cell function.