Causal Association Between Immune Cells and Cardiac Arrest: A Mendelian Randomization Study
Abstract
Objective: To analyze the potential causal association between 731 immune cell phenotypes and cardiac arrest (CA) using the Mendelian randomization (MR) method. Methods: GWAS statistical data (GCST90001391–GCST90002121) for 731 immune cell phenotypes were obtained from the GWAS Catalog database, and cardiac arrest data were obtained from the FinnGen genomics research project dataset (I9_CARDARR). Single-nucleotide polymorphisms (SNPs) were used as instrumental variables for MR analysis. To assess the causal link between 731 immune cell phenotypes and CA, we employed several Mendelian randomization (MR) techniques, including inverse variance weighted, MR-Egger regression, weighted median, simple mode, and weighted mode, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The Cochran Q test was used to assess heterogeneity, MR-Egger regression and MR-PRESSO tests were used to assess horizontal pleiotropy, and the “leave-one-out” method was used to assess the sensitivity of individual SNPs to causal estimation results. Results: MR analysis revealed a causal association between 33 immune cell phenotypes and CA (P < 0.05), with significant positive causal associations (P < 0.01) observed for Natural Killer %lymphocyte [OR = 1.080, 95%CI (1.023, 1.140), P < 0.01], CD3 on T cell [OR = 1.058, 95%CI (1.104, 1.103), P < 0.01], and CD127 on granulocyte [OR = 1.120, 95%CI (1.044, 1.202), P < 0.01] with CA. There is a significant negative causal relationship (P < 0.01) between the percentage of CD39+ secreting CD4 regulatory T cells among CD4 regulatory T cells [OR = 0.940, 95%CI (0.897, 0.984), P < 0.01], the percentage of CD8+ and CD8dim T cells among leukocytes [OR = 0.825, 95%CI (0.726, 0.939), P < 0.01], the percentage of CD39+ CD8+ T cells among CD8+ T cells [OR = 0.919, 95%CI (0.866, 0.975), P < 0.01], and CD3 on Effector Memory CD8+ T cells [OR = 0.888, 95%CI (0.826, 0.955), P < 0.01] and cardiac arrest (CA). The absence of significant heterogeneity and horizontal pleiotropy was confirmed by the Cochran Q test, MR-Egger regression, and MR-PRESSO test (all P > 0.05), supporting the validity of the inferred causal relationship between the immune cell phenotypes and CA. The results of the reverse MR analysis were not statistically significant (P > 0.05), supporting a unidirectional causal relationship between immune cell phenotypes and CA. Conclusion: Natural Killer %lymphocyte, CD3 on T cell, and CD127 on granulocyte may be risk factors for CA, while CD39+ secreting CD4 regulatory T cell %CD4 regulatory T cell, CD8+ and CD8dim T cell %leukocyte, CD39+ CD8+ T cell %CD8+ T cell, and CD3 on Effector Memory CD8+ T cell may have a protective effect against CA.
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