Causal effects of 731 immune cells on post-traumatic stress disorder: A Mendelian randomization study

The involvement of immune cells in the pathogenesis of post-traumatic stress disorder (PTSD) remains incompletely understood. This study aims to evaluate the causal effect of immune cells on PTSD by Mendelian randomization (MR). Datasets of 731 immune cells, numbered from GCST0001391 to GCST0002121, were obtained from European Bioinformatics Institute, and datasets of PTSD, numbered finngen_R10_F5_PTSD, were acquired from FinnGen. Single nucleotide polymorphisms meeting the criterion were screened according to the association, independence, and exclusivity hypotheses. Inverse variance weighted was used as the primary method of MR analysis to assess the causal relationship between immune cells and PTSD. MR-Egger intercept was employed to assess the horizontal pleiotropy of the results. Cochran Q test and leave-one-out sensitivity analysis were conducted to assess the heterogeneity and robustness of the outcomes, respectively. The MR analysis showed that IgD- CD27- %B cell (odds ratio [OR] 1.151, 95% confidence interval [CI] 1.002-1.322, P = .047), IgD on transitional (OR 1.117, 95% CI 1.019-1.225, P = .018), IgD on IgD + CD38br (OR 1.074, 95% CI 1.003-1.149, P = .040), CD25 on IgD + CD38br (OR 1.186, 95% CI 1.014-1.388, P = .033), CD25 on transitional (OR 1.272, 95%CI 1.054-1.534, P = .012), CD3 on HLA-DR + CD8br (OR 1.219, 95%CI 1.031-1.440, P = .020), and CD24 + CD27+ %lymphocyte (OR 1.249, 95%CI 1.001-1.558, P = .049) were associated with increased genetic susceptibility to PTSD. MR-Egger intercept revealed no evidence of horizontal pleiotropy (P ≥ .05). Cochran Q demonstrated the absence of heterogeneity (P ≥ .05). Leave-one-out sensitivity analysis indicated that the results were robust. Our analysis indicated that IgD- CD27- %B cell, IgD on transitional, IgD on IgD + CD38br, CD25 on IgD + CD38br, CD25 on transitional, CD3 on HLA-DR + CD8br, and CD24 + CD27+ %lymphocyte were associated with increased genetic susceptibility to PTSD. It provides new insights for pathogenesis of PTSD.