Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Pediatric Neurosurgery, West China Women's and Children's Hospital, Sichuan University West China Second University Hospital, Chengdu, China.
Brain Behav. 2024 May;14(5):e3532. doi: 10.1002/brb3.3532.
Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis.
Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome-wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave-one-out analysis.
For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011-1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045-1.511, p = .015).
Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.
神经认知和精神障碍已被证明比一般人群更容易与特发性正常压力脑积水（iNPH）共病。然而，这些疾病与 iNPH 之间的潜在因果关系尚未得到评估。因此，我们的研究旨在基于双向孟德尔随机化（MR）分析来研究它们之间的因果关系。
采用逆方差加权（IVW）方法的随机效应来获得神经认知障碍、精神障碍和 iNPH 之间的因果关系。通过 OpenGWAS 数据库、GWAS Catalog 和精神基因组学联合会下载了 12 种神经认知和精神障碍的全基因组关联研究（GWAS）数据，而 iNPH 的 GWAS 数据则来自 FinnGen 联合会第 9 轮发布，其中有 767 例病例和 375610 例欧洲血统对照。我们还使用加权中位数模型、Cochrane's Q 检验、MR-Egger 回归、MR 偏倚残差总和和异常值检测以及单样本分析对这些显著因果推断进行了敏感性分析。
对于大多数神经认知和精神障碍，没有发现它们与 iNPH 之间存在因果关系。我们发现 iNPH（比值比[OR] = 1.030，95%置信区间[CI]：1.011-1.048，p =.001）与精神分裂症风险增加相关，但在敏感性分析中未得到验证。值得注意的是，遗传预测的帕金森病（PD）与 iNPH 的风险增加相关（OR = 1.256，95% CI：1.045-1.511，p =.015）。
我们的研究揭示了 PD 与 iNPH 风险增加之间存在潜在的因果关系。需要进一步研究来探讨 PD 与 iNPH 之间的关联和潜在的机制。
