PDF(Pubmed)
Abstract：
Studies have suggested that blood circulating phytosterols, plant-derived sterols analogous to cholesterol, were associated with blood lipid levels and the risk of Alzheimer\'s disease (AD) and Parkinson\'s disease (PD). This Mendelian randomization (MR) study is performed to determine the causal effect of circulating phytosterols on AD and PD and evaluate the mediation effect of blood lipids.
Leveraging genome-wide association studies summary-level data for phytosterols, blood lipids, AD, and PD, univariable and multivariable MR (MVMR) analyses were conducted. Four types of phytosterols (brassicasterol, campesterol, sitosterol, and stigmasterol), three blood lipids parameters (high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and triglyceride), two datasets for AD and PD were used. Inverse-variance weighted method was applied as the primary analysis, and false discovery rate method was used for adjustment of multiple comparisons.
Using the largest AD dataset, genetically proxied higher levels of stigmasterol (OR = 0.593, 95%CI = 0.431-0.817, P = 0.004) and sitosterol (OR = 0.864, 95%CI = 0.791-0.943, P = 0.004) significantly correlated with a lower risk of AD. No significant associations were observed between all four types of phytosterols levels and PD. MVMR estimates showed that the above causal associations were missing after integrating the blood lipids as exposures. Sensitivity analyses confirmed the robustness of these associations, with no evidence of pleiotropy and heterogeneity.
The study supports a potential beneficial role of blood stigmasterol and sitosterol in reducing the risk of AD, but not PD, which is dependent on modulating blood lipids. These insights highlight circulating stigmasterol and sitosterol as possible biomarkers and therapeutic targets for AD.
Leveraging genome-wide association studies summary-level data for phytosterols, blood lipids, AD, and PD, univariable and multivariable MR (MVMR) analyses were conducted. Four types of phytosterols (brassicasterol, campesterol, sitosterol, and stigmasterol), three blood lipids parameters (high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and triglyceride), two datasets for AD and PD were used. Inverse-variance weighted method was applied as the primary analysis, and false discovery rate method was used for adjustment of multiple comparisons.
Using the largest AD dataset, genetically proxied higher levels of stigmasterol (OR = 0.593, 95%CI = 0.431-0.817, P = 0.004) and sitosterol (OR = 0.864, 95%CI = 0.791-0.943, P = 0.004) significantly correlated with a lower risk of AD. No significant associations were observed between all four types of phytosterols levels and PD. MVMR estimates showed that the above causal associations were missing after integrating the blood lipids as exposures. Sensitivity analyses confirmed the robustness of these associations, with no evidence of pleiotropy and heterogeneity.
The study supports a potential beneficial role of blood stigmasterol and sitosterol in reducing the risk of AD, but not PD, which is dependent on modulating blood lipids. These insights highlight circulating stigmasterol and sitosterol as possible biomarkers and therapeutic targets for AD.
摘要：
背景：研究表明，血液循环中的植物甾醇，类似于胆固醇的植物来源的甾醇，与血脂水平和阿尔茨海默病（AD）和帕金森病（PD）的风险有关。进行此孟德尔随机化（MR）研究以确定循环植物甾醇对AD和PD的因果作用，并评估血脂的介导作用。
方法：利用植物甾醇的全基因组关联研究汇总水平数据，血脂,AD,还有PD,进行了单变量和多变量MR（MVMR）分析。四种类型的植物甾醇(油菜甾醇，菜油甾醇,谷甾醇,和豆甾醇)，三个血脂参数(高密度脂蛋白胆固醇[HDL-C]，非HDL-C,和甘油三酯），使用了AD和PD的两个数据集.采用逆方差加权法作为主要分析，并采用错误发现率法进行多重比较的调整。
结果：使用最大的AD数据集，较高的前甾醇水平(OR=0.593,95CI=0.431-0.817,P=0.004)和谷甾醇水平(OR=0.864,95CI=0.791-0.943,P=0.004)与较低的AD风险显著相关。在所有四种类型的植物甾醇水平和PD之间没有观察到显著的关联。MVMR估计表明，将血脂整合为暴露量后，上述因果关系缺失。敏感性分析证实了这些关联的稳健性，没有多效性和异质性的证据。
结论：该研究支持血豆甾醇和谷甾醇在降低AD风险方面的潜在有益作用。但不是警局,依赖于调节血脂。这些见解突出了循环的豆甾醇和谷甾醇作为AD的可能的生物标志物和治疗靶标。
方法：利用植物甾醇的全基因组关联研究汇总水平数据，血脂,AD,还有PD,进行了单变量和多变量MR（MVMR）分析。四种类型的植物甾醇(油菜甾醇，菜油甾醇,谷甾醇,和豆甾醇)，三个血脂参数(高密度脂蛋白胆固醇[HDL-C]，非HDL-C,和甘油三酯），使用了AD和PD的两个数据集.采用逆方差加权法作为主要分析，并采用错误发现率法进行多重比较的调整。
结果：使用最大的AD数据集，较高的前甾醇水平(OR=0.593,95CI=0.431-0.817,P=0.004)和谷甾醇水平(OR=0.864,95CI=0.791-0.943,P=0.004)与较低的AD风险显著相关。在所有四种类型的植物甾醇水平和PD之间没有观察到显著的关联。MVMR估计表明，将血脂整合为暴露量后，上述因果关系缺失。敏感性分析证实了这些关联的稳健性，没有多效性和异质性的证据。
结论：该研究支持血豆甾醇和谷甾醇在降低AD风险方面的潜在有益作用。但不是警局,依赖于调节血脂。这些见解突出了循环的豆甾醇和谷甾醇作为AD的可能的生物标志物和治疗靶标。
