The association between schizophrenia and white blood cells count: a bidirectional two-sample Mendelian randomization study

Abstract

Abstract Background. Positive associations between the risk of schizophrenia and white blood cells (WBC) counts, have been suggested by observational studies. However, the causality of this association is still unclear. Methods. We used a group of bidirectional two-sample Mendelian randomization (MR) analyses to estimate the causal relationship between schizophrenia and WBC count traits (i.e., WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count). In total, 81, 95, 85, 87, 76, 83 schizophrenia-related single nucleotide polymorphisms (SNPs) were used as genetic instruments from Psychiatric Genomics Consortium for six WBC count traits, respectively. And in reverse MR analysis, 458, 206, 408, 468, 473, 390 variants extracted from six WBC count traits were utilized as genetic instruments, which were obtained from a recent large-scale Genome-Wide Association Study (GWAS). Results. Genetically predicted schizophrenia was positively associated with the risk of WBC count [odds ratio (OR) 1.017, 95% confidence interval (CI) 1.008–1.026; P = 7.53×10− 4], basophil count (OR 1.014, 95%CI 1.005–1.022; P = 0.002), eosinophil count (OR 1.021, 95%CI 1.011–1.031; P = 2.77×10− 4), monocyte count(OR 1.018, 95%CI 1.009–1.027; P = 4.60×10− 4), lymphocyte count(OR 1.021, 95%CI 1.012–1.030; P = 4.51×10− 5), and neutrophil count (OR 1.013, 95%CI 1.005–1.022; P = 0.004). WBC count traits are not associated with the risk of schizophrenia in our reverse MR results. Conclusion. Schizophrenia is associated with increased risk of WBC count (i.e., high WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count).