Bidirectional causal association between ischemic stroke and five mental disorders

Abstract

Objective: To explore the bidirectional causal association between ischemic stroke and five mental disorders from a genetic perspective using two-sample Mendelian randomization (TSMR).

Methods: Single-nucleotide polymorphisms (SNPs) associated with ischemic stroke were obtained from the genome-wide association study (GWAS) database, and those closely related to the exposure phenotype and satisfying the three core assumptions of Mendelian randomization were selected as instrumental variables (IVs). The main TSMR analysis was conducted using the inverse variance-weighted (IVW) method, and the robustness of the results was assessed using the weighted median, weighted mode, and MR Egger methods. Heterogeneity test, pleiotropy test, and sensitivity analysis were also conducted to further ensure the accuracy and stability of the research results.

Results: This study found a positive correlation between ischemic stroke and depression [IVW method (FEM): OR = 1.002, 95%CI: 1.000-1.003, P = 0.023<0.05], but no significant causal association with schizophrenia, bipolar disorder, insomnia, or anxiety (P > 0.05). Reverse TSMR analysis showed no causal association between depression, schizophrenia, bipolar disorder, insomnia, anxiety, and ischemic stroke (P > 0.05).

Conclusion: This study used TSMR to demonstrate from a genetic perspective that there is a positive correlation between ischemic stroke and depression, which increases the risk of depression. Proactive intervention for ischemic stroke might reduce the risk of depression.

Keywords: anxiety; depression; insomnia; ischemic stroke; schizophrenia.