Causal associations between immune cells and psychiatric disorders: a bidirectional mendelian randomization analysis.

Extensive researches illuminate a potential interplay between immune traits and psychiatric disorders. However, whether there is the causal relationship between the two remains an unresolved question. We conducted a two-sample bidirectional mendelian randomization by utilizing summary data of 731 immune cell traits from genome-wide association studies (GCST90001391-GCST90002121)) and 11 psychiatric disorders including attention deficit/hyperactivity disorder (ADHD), anxiety disorder, autism spectrum disorder (ASD), bipolar disorder (BIP), anorexia nervosa (AN), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), Tourette syndrome (TS), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), and substance use disorders (cannabis) (SUD) from the Psychiatric Genomics Consortium (PGC). A total of four types of immune signatures (median fluorescence intensities [MFI], relative cell [RC], absolute cell [AC], and morphological parameters [MP]) were included. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weighted median method, Mendelian randomization (MR)-Egger, and corrected by false discovery rate. Outliers were evaluated through the leave-one-out technique. Horizontal pleiotropy was assessed using the MR pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger intercept tests. MR analysis results suggested several immune cell subtypes were casually associated with psychiatric disorders. It was found that CD33br HLA DR + CD14 - AC (Myeloid cell, AC) may contribute to decreasing the risk of BIP (odds ratio [OR] = 0.9179, confidence interval [CI] = 0.8829-0.9542, P = 7.06 × 10), and likewise, CD38 on transitional (B cell, MFI) also showed negative causal effect on SCZ risk (OR = 0.9551, CI = 0.9330-0.9776, P = 0.0441). While IgD - CD27 - %lymphocyte (B cell, RC) has causal effect on increasing BIP risk (OR = 1.0184, CI = 1.0079-1.0291, P = 0.0201). In addition, HLA DR + + monocyte %monocyte (TBNK, RC) is likely to increase AN onset (OR = 1.0746, CI = 1.0324-1.1186, P = 0.0506), and CCR2 on CD14 - CD16 + monocyte (Monocyte, MFI) may contribute to PTSD (OR = 1.0591, CI = 1.0275-1.0917, P = 0.0369). Sensitivity analysis revealed consistency of results. Our research elucidates there may be causal links between immune traits and the onset of psychiatric disorders, which established a groundwork for the prospective clinical utilization of immune cells as markers for the diagnosis and early intervention of psychiatric disorders.