ObjectiveObservational 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). MethodsA 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. ResultsMR-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. ConclusionThere 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.
ObjectiveTo investigate the relationship between neuroticism and functional gastrointestinal disorders using Mendelian randomized (MR). MethodsBased on the genome-wide association study data of neuroticism and 2 functional gastrointestinal disorders, i.e., functional dyspepsia (FD), and irritable bowel syndrome (IBS), appropriate single nucleotide polymorphisms (SNP) were extracted as instrumental variables, and inverse variance weighted (IVW) was applied as the main analysis method, and sensitivity analyses were performed by Cochran’s Q test, MR-PRESSO test, MR-Egger intercept, and leave one out analysis. Further two-step MR analyses were performed to examine the mediating effects of coffee intake, alcohol consumption, smoking, depression. ResultsThe univariable MR analysis showed that genetically determined neuroticism was positively causally associated with the risk of developing FD and IBS (FD: OR=1.448, 95%CI 1.057 to 1.983, P=0.021; IBS: OR=1.705, 95%CI 1.210 to 2.403, P=0.002). Cochran's Q-test, MR-Egger intercept, MR-PRESSO did not observe significant heterogeneity or horizontal pleiotropy. Leave-one-out analyses also did not find a large effect of individual SNPs on the overall results. Multivariable MR analyses showed that the association between neurotic personality and elevated risk of FD and IBS prevalence persisted even after adjusting for other confounders. Further two-step MR mediation analyses revealed that depression partially mediated this effect, with mediation proportions of 59.41% (95%CI 5.69% to 113.12%) and 67.53% (95%CI 31.55% to 103.51%), respectively. ConclusionThere is a degree of causal association between neuroticism and FD and IBS, and depression may play an important mediating role in this association.