Mendelian randomization and mediation examination of the immune cell-mediated link between sphingomyelin and stroke

Objective

The study established a direct link between stroke and sphingomyelin. The precise biology underlying this connection is yet unknown, though. As a result, we decided to investigate the potential causal relationship between Sphingomyelin and genetic vulnerability to stroke, as well as the potential mediating function that immune cells may play in this process, using Mendelian randomization (MR) approaches.

Methods

A published genome-wide association study (GWAS) dataset of European populations served as the foundation for the MR Study. The inverse variance weighting (IVW) model is the main technique. Four additional statistical techniques (MR Egger, Weighted median, Simple mode, and Weighted mode) were also employed to enhance the verification process. Reverse MR Analysis was utilized to reinforce the findings, and heterogeneity and horizontal pleipotency were assessed. Additionally, this study looked into potential immune cell mediating roles in the causal link between sphingomyelin and stroke using two-step MR techniques.

Result

The IVW metod's results indicated that sphingomyelin genetic susceptibility was linked to a high risk of stroke (OR = 1.045 [95 %CI, 1.004–1.087; P = 0.031). Additionally, the statistical result of SSC−A on CD8br and stroke was IVW [P = 0.007, OR(95 % CI) 1.020 (1.005–1.034)], which was proportionate to the increased risk of stroke. A lower incidence of stroke IVW is linked to CD45 on CD8br [P = 0.004, OR(95 % CI) 0.993 (0.988-0.998)]. Furthermore, our results imply that SSC−A on CD8br and CD45 on CD8br contribute to the causative relationship between sphingomyelin and stroke. The percentages of conciliation are 5.38 %, 22.7 %, 33.5 %), and 0.000999, 0.0152, 0.0132, respectively.

Conclusion

We confirmed the effect of sphingomyelin on stroke and conducted in-depth studies. SSC−A on CD8br and CD45 on CD8br is latent stroke mediators associated with sphingomyelin. Through two-step mediated Mendelian randomization analysis, we provide new insights into the etiology and treatment of stroke.