PDF(Pubmed)
Abstract：
BACKGROUND: Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization.
METHODS: Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests.
RESULTS: The Cochran\'s Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results.
CONCLUSIONS: This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.
METHODS: Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests.
RESULTS: The Cochran\'s Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results.
CONCLUSIONS: This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.
摘要：
背景：观察性研究表明恐慌症（PD）和阿尔茨海默病（AD）之间存在联系。本研究旨在使用孟德尔随机化确定PD与AD风险的潜在关联。
方法：在PD和AD之间的全基因组关联研究中检索了遗传工具变量（IVs）。然后，五种不同的模型，即方差逆加权(IVW)，加权中位数，加权模式，MR-Egger和MR稳健调整轮廓评分(MR-RAPS)，用于MR分析。最后,通过多重敏感性试验验证了已鉴定IVs的异质性和多效性.
结果：基于MREgger和IVW的Cochran\'sQ检验表明，在工具变量的影响中没有发现异质性的证据，所以使用了固定效应模型。IVW分析（OR1.000479，95%CI[1.000147056，1.000811539]，p=0.005）表明PD与AD风险增加相关，它们之间存在因果关系。同时,加权中位数(OR1.000513373，95%CI[1.000052145，1.000974814]，p=0.029）和MR-RAPS（或1.000510118，95%CI[1.000148046，1.00087232]，p=0.006)也显示了类似的发现。此外,广泛的灵敏度分析证实了这些结果的鲁棒性和准确性。
结论：这项调查提供了PD与AD风险增加之间潜在因果关系的证据。根据我们的MR结果,在诊断和治疗PD患者时，临床医师应更多关注AD相关症状,选择治疗措施或尽量减少合并症.此外，同时改善PD和AD的药物的开发可能更好地治疗这些合并症患者.
方法：在PD和AD之间的全基因组关联研究中检索了遗传工具变量（IVs）。然后，五种不同的模型，即方差逆加权(IVW)，加权中位数，加权模式，MR-Egger和MR稳健调整轮廓评分(MR-RAPS)，用于MR分析。最后,通过多重敏感性试验验证了已鉴定IVs的异质性和多效性.
结果：基于MREgger和IVW的Cochran\'sQ检验表明，在工具变量的影响中没有发现异质性的证据，所以使用了固定效应模型。IVW分析（OR1.000479，95%CI[1.000147056，1.000811539]，p=0.005）表明PD与AD风险增加相关，它们之间存在因果关系。同时,加权中位数(OR1.000513373，95%CI[1.000052145，1.000974814]，p=0.029）和MR-RAPS（或1.000510118，95%CI[1.000148046，1.00087232]，p=0.006)也显示了类似的发现。此外,广泛的灵敏度分析证实了这些结果的鲁棒性和准确性。
结论：这项调查提供了PD与AD风险增加之间潜在因果关系的证据。根据我们的MR结果,在诊断和治疗PD患者时，临床医师应更多关注AD相关症状,选择治疗措施或尽量减少合并症.此外，同时改善PD和AD的药物的开发可能更好地治疗这些合并症患者.
