Causal role of immune cell traits in stroke: A Mendelian randomization study.

OBJECTIVES:Immune mechanisms play a crucial role in the development of stroke. However, immune-related phenotypes are diverse and their associations with stroke are largely unknown. Here, we aimed to systematically explore the causal role of immune cell traits in stroke and its subtypes by leveraging data from genome-wide association studies (GWASs). MATERIALS AND METHODS:Exposure data were obtained from a recent GWAS on 731 immune cell traits profiled by flow cytometry involving 3757 individuals. By conducting two-sample univariable Mendelian randomization (MR) analyses, each immune cell trait was assessed for causal relationships with stroke outcomes from the MEGASTROKE Consortium (40,585 cases and 406,111 controls). The robustness of the MR results was verified by a series of sensitivity analyses. RESULTS:We identified three significant associations after Bonferroni correction (P < 1.37E-05). Increased CD27 expression on memory B cell (OR = 1.23, 95% CI = 1.14-1.33, P = 2.78E-08), IgD-CD38dim B cell (OR = 1.16, 95% CI = 1.09-1.23, P = 5.98E-06) and unswitched memory B cell (OR = 1.18, 95% CI = 1.10-1.27, P = 1.09E-05) were associated with a higher risk of large-artery atherosclerotic stroke (LAS). Furthermore, expression quantitative trait loci data also indicated elevated blood CD27 mRNA level was a risk factor for LAS (OR = 1.37, 95% CI = 1.02-1.84, P = 0.037). CONCLUSIONS:This study provided genetic evidence of the causal relationship between immune cell traits and stroke, highlighting the role of CD27 on memory B cell as a novel factor for LAS risk.