Causal relationship between immune cells and myocardial infarction: A Mendelian randomization study

Myocardial infarction (MI) is a major cause of death worldwide. It is been suspected for a long time that MI is linked to immune cells. However, observational studies are plagued by confounding factors and reverse causality, whether the immune response is a cause or consequence of MI remains unknown. The present study aimed to determine whether genetically immune cells might have a causal effect on MI. According to publicly available genetic data, we assessed the causal relationship between 731 immune cell signatures (7 groups) and MI based on a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms from a genome-wide association study comprising 3757 Sardinians on immune cells were used as exposure instruments. Another summary-level genome-wide association study statistics of MI were used as the outcome data. We primarily used inverse variance weighted, MR-egger, and simple median methods to perform MR analyses. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. Twenty-seven of 731 immune cell phenotypes are causally associated with MI (odds ratio: 0.94-1.06, 95% confidence interval: 0.80-1.15, P < .048). Among them, 14 immunophenotypes were negatively associated with the occurrence of MI, in other words, the more these immune cell phenotypes, the lower the probability of MI. The remaining 13 immunophenotypes were positively correlated with MI. Our study has demonstrated the close connection between immune cells and MI by genetic means, and revealed the direct causal relationship between these immune cells and MI with the help of MR experiments, which to a certain extent avoids the wastage of manpower, resources, and finance that would be incurred by opening up a large-scale clinical trial to obtain unsatisfactory results. On the other hand, these immune cells shown in our results may become new biomarkers of MI or even potential drug targets for the treatment of MI, thus providing a new target for prevention, diagnosis, and treatment of MI.