Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China.
Acta Psychiatr Scand. 2023 Oct;148(4):359-367. doi: 10.1111/acps.13606. Epub 2023 Sep 4.
To explore the bidirectional causal association between ischemic stroke and five mental disorders from a genetic perspective using two-sample Mendelian randomization (TSMR).
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.
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).
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.
从遗传角度出发,利用两样本 Mendelian 随机化(TSMR)探索缺血性中风与五种精神障碍之间的双向因果关系。
从全基因组关联研究(GWAS)数据库中获取与缺血性中风相关的单核苷酸多态性(SNP),并选择与暴露表型密切相关且满足 Mendelian 随机化三个核心假设的 SNP 作为工具变量(IVs)。主要 TSMR 分析采用逆方差加权(IVW)法进行,采用加权中位数、加权模式和 MR Egger 法评估结果的稳健性。还进行了异质性检验、多效性检验和敏感性分析,以进一步确保研究结果的准确性和稳定性。
本研究发现缺血性中风与抑郁症之间存在正相关[IVW 法(FEM):OR=1.002,95%CI:1.000-1.003,P=0.023<0.05],但与精神分裂症、双相情感障碍、失眠或焦虑无显著因果关系(P>0.05)。反向 TSMR 分析显示,抑郁症、精神分裂症、双相情感障碍、失眠、焦虑与缺血性中风之间无因果关系(P>0.05)。
本研究采用 TSMR 从遗传角度证明,缺血性中风与抑郁症之间存在正相关,这增加了患抑郁症的风险。对缺血性中风的积极干预可能会降低患抑郁症的风险。