目的 观察性研究表明血浆脂质与神经退行性疾病(NDD)发病具有相关性,但因果关系尚不明确.本研究利用两样本孟德尔随机化(MR)探讨不同血浆脂质体与主要NDD之间的因果联系.方法 采用两样本MR方法分析179种脂质体与阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS)和多发性硬化症(MS)等主要NDD的因果关系,运用逆方差加权法(IVW)作为主要分析方法,并采用多种敏感性分析以保证主要分析结果的可靠性.结果 MR-IVW结果显示:磷脂酰乙醇胺(PE)[OR=0.90,95％CI(0.83,0.99),P=0.03]、磷脂酰胆碱(PC)[OR=0.92,95％CI(0.85,0.99),P=0.02]和磷脂酰肌醇(PI)[OR=0.90,95％CI(0.83,0.99),P=0.03]能够降低 AD 的发病风险;甾醇酯[OR=1.18,95％CI(1.04,1.34),P=0.01]和胆固醇[OR=1.26,95％CI(1.02,1.56),P=0.03]增加 PD 的发病风险,PE[OR=0.79,95％CI(0.64,0.98),P=0.03]和 PC[OR=0.83,95％CI(0.69,0.98),P=0.03]能够降低 PD 的发病风险;二酰基甘油(DAG)[OR=1.24,95％CI(1.01,1.54),P=0.04]和鞘磷脂(SM)[OR=1.13,95％CI(1.08,1.58),P=0.01]是 MS 的危险因素,PI[OR=0.77,95％CI(0.62,0.95),P=0.02]和 PC[OR=0.74,95％CI(0.58,0.95),P=0.02]是 MS 的保护因素,PI[OR=1.02,95％CI(1.01,1.04),P=0.02]和甘油三酯(TG)[OR=1.03,95％CI(1.01,1.05),P=0.02]增加 ALS 的发病风险,PC[OR=0.98,95％CI(0.97,0.99),P=0.03]降低ALS的发病风险.结论 甾醇酯、胆固醇、PC、PE、PI、DAG、SM、TG和不同NDD之间存在因果联系,这将为后续更多临床研究提供理论依据和支持.
Causality between plasma lipids and neurodegenerative diseases:a bidirectional two-sample Mendelian randomization analysis
Objective Observational studies have shown that plasma lipids are associated with the development of neurodegenerative diseases(NDD),but the causal relationship is unclear.This study investigated the causal relationship between 179 liposomes and NDD using a two-sample Mendelian randomization(MR).Methods A two-sample MR method was used to comprehensively analyze the causal relationship between liposomes and major NDD such as Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS)and multiple sclerosis(MS).The two sample software package and Phenoscanner database were used to screen for appropriate instrumental variables(TV).In this study,inverse variance weighting(IVW)was used as the primary measure of MR analysis,and various sensitivity tests were performed.Results MR-IVW results showed that phosphatidylethanolamine(PE)(OR=0.90,95％CI 0.83 to 0.99,P=0.03),phosphatidylcholine(PC)(OR=0.92,95％CI 0.85 to 0.99,P=0.02)and phosphatidylinositol(PI)(OR=0.90,95％CI 0.83 to 0.99,P=0.03)were protective factors for AD.Sterol ester(OR=1.18,95％CI 1.04 to 1.34,P=0.01)and cholesterol(OR=1.26,95％CI 1.02 to 1.56,P=0.03)increased the risk of PD.PE(OR=0.79,95％CI 0.64 to 0.98,P=0.03)and PC(OR=0.83,95％CI 0.69 to 0.98,P=0.03)reduced the risk of PD.Diacylglycerol(DAG)(OR=1.24,95％CI 1.01 to 1.54,P=0.04)and sphingomyelin(SM)(OR=1.13,95％CI 1.08 to 1.58,P=0.01)were the risk factors for MS.PI(OR=0.77,95％CI 0.62 to 0.95,P=0.02)and PC(OR=0.74,95％CI 0.88 to 0.95,P=0.02)were protective factors for MS.PI(OR=1.02,95％CI 1.01 to 1.04,P=0.02)and triglyceride(TG)(OR=1.03,95％CI 1.01 to 1.05,P=0.02)increased the risk of ALS,PC(OR=0.98,95％CI 0.97 to 0.99,P=0.03)decreased the risk of ALS.Conclusion There is a causal relationship between sterol ester,cholesterol,PC,PE,PI,DAG,SM,TG and different NDD,which provides a theoretical basis and support for further clinical studies.
万方数据
维普
