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Purpose: This research employed Mendelian randomization (MR) methods to explore whether metabolites are causally associated with embolic stroke of undetermined source (ESUS). Methods: Genome-Wide Association Study (GWAS) data regarding metabolites and ESUS were downloaded from the database. Metabolites were employed as exposure factors, ESUS served as the outcome variable, and single nucleotide polymorphisms (SNPs) exhibiting significant association with ESUS were chosen as instrumental variables. The causal association between exposure factor metabolites and the outcome variable ESUS was assessed using two methods: MR-Egger regression and inverse variance-weighted (IVW) analysis. Results: A causal relationship was observed between X-11593--Omethylascorbate* and ESUS, indicating a protective factor. Moreover, a causal relationship was identified between cholesterol esters in large very-low-density lipoprotein (VLDL), cholesterol esters in medium low-density lipoprotein (LDL), concentration of medium LDL particles, phospholipids in medium LDL, phenylalanine, total cholesterol in small LDL, total lipids in medium LDL and ESUS, representing risk factor. Funnel plots exhibited a symmetrical distribution of SNPs, while pleiotropic tests (p > 0.05) and leave-one-out tests indicated that the results were relatively stable. Conclusion: Metabolites are causally associated with ESUS. LDL and VLDLrelated metabolites are identified as risk factors for ESUS. [ABSTRACT FROM AUTHOR]

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BackgroundThe relationship between gut microbiota composition and coronary heart disease (CHD) has been recently reported in several observational studies. However, the causal effect of gut microbiota on coronary heart disease is uncharted.ObjectiveThis study attempted to investigate the effect of gut microbiota on coronary heart disease by Mendelian randomization (MR) analysis.MethodsThrough the two-sample MR method, single-nucleotide polymorphisms relevant to gut microbiota were selected as instrument variables to evaluate the causal association between gut microbiota and the risk of CHD.ResultsAccording to the selection criteria of the inverse variance-weighted average method, Class Actinobacteria, Class Lentisphaeria, Family Clostridiales vadinBB60group, Genus Clostridium innocuum group, Genus Bifidobacterium, Genus Butyricicoccus, Genus Oxalobacter, Genus Turicibacter, and Order Victivallales, presented a suggestive association with coronary heart disease.ConclusionThis two-sample Mendelian randomization study found that gut microbiota was causally associated with coronary heart disease. Further randomized controlled trials are needed to clarify the protective effect of probiotics on coronary heart disease and their specific protective mechanisms.

Purpose: This research employed Mendelian randomization (MR) methods to explore whether metabolites are causally associated with embolic stroke of undetermined source (ESUS)., Methods: Genome-Wide Association Study (GWAS) data regarding metabolites and ESUS were downloaded from the database. Metabolites were employed as exposure factors, ESUS served as the outcome variable, and single nucleotide polymorphisms (SNPs) exhibiting significant association with ESUS were chosen as instrumental variables. The causal association between exposure factor metabolites and the outcome variable ESUS was assessed using two methods: MR-Egger regression and inverse variance-weighted (IVW) analysis., Results: A causal relationship was observed between X-11593--O-methylascorbate* and ESUS, indicating a protective factor. Moreover, a causal relationship was identified between cholesterol esters in large very-low-density lipoprotein (VLDL), cholesterol esters in medium low-density lipoprotein (LDL), concentration of medium LDL particles, phospholipids in medium LDL, phenylalanine, total cholesterol in small LDL, total lipids in medium LDL and ESUS, representing risk factor. Funnel plots exhibited a symmetrical distribution of SNPs, while pleiotropic tests ( p  > 0.05) and leave-one-out tests indicated that the results were relatively stable., Conclusion: Metabolites are causally associated with ESUS. LDL and VLDL-related metabolites are identified as risk factors for ESUS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hang, Chen, Ren, Wang, Zhu and Zhu.)

• Mendelian randomization was used to assess the association between CRP and cognitive impairment. • Genetically proxied CRP may be associated with prospective memory. • CRP may have a potential effect on cognitive impairment, suggesting that anti-inflammatory strategies may have an adverse effect on cognitive impairment. While C-reactive protein (CRP) has been solidly linked as a risk factor for cognitive impairment, observational research alone cannot definitively demonstrate a causal relationship. This study therefore sought to determine whether there was an association between CRP and the development of cognitive impairment. This study employed bidirectional Mendelian randomization (MR) to investigate the genetic association between CRP and cognitive impairment. genome-wide association studies (GWAS) summary statistics for both were sourced from IEU Open GWAS or prior reports. Cognitive GWAS's used were on tests designed to assess cognitive performance, fluid intelligence, prospective memory, and reaction time. The MR analysis applied several methods, including inverse variance-weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode approaches, then use of MR sensitivity analyses to interrogate findings. Forward MR analysis showed that genetically proxied CRP was associated with prospective memory (P = 0.009), whereas there is little evidence to support an association between CRP and other cognitive tests. Reverse MR analysis indicated a potential association between genetic proxy cognitive performance (P = 0.002) and fluid intelligence score (P = 0.019) with CRP levels. For genetically proxied CRP on prospective memory, the level of pleiotropy (P > 0.05) and no genetic variant heterogeneity (P > 0.05) made bias unlikely, and leave-one-out tests also confirmed robust associations. The effect of genetically proxied CRP on prospective memory, with little evidence on other cognitive tests. The reverse MR shows some evidence of genetically proxied cognition (cognitive performance and fluid intelligence) on CRP levels. [ABSTRACT FROM AUTHOR]

Background: The relationship between gut microbiota composition and coronary heart disease (CHD) has been recently reported in several observational studies. However, the causal effect of gut microbiota on coronary heart disease is uncharted., Objective: This study attempted to investigate the effect of gut microbiota on coronary heart disease by Mendelian randomization (MR) analysis., Methods: Through the two-sample MR method, single-nucleotide polymorphisms relevant to gut microbiota were selected as instrument variables to evaluate the causal association between gut microbiota and the risk of CHD., Results: According to the selection criteria of the inverse variance-weighted average method, Class Actinobacteria, Class Lentisphaeria, Family Clostridiales vadinBB60group, Genus Clostridium innocuum group, Genus Bifidobacterium , Genus Butyricicoccus , Genus Oxalobacter , Genus Turicibacter , and Order Victivallales, presented a suggestive association with coronary heart disease., Conclusion: This two-sample Mendelian randomization study found that gut microbiota was causally associated with coronary heart disease. Further randomized controlled trials are needed to clarify the protective effect of probiotics on coronary heart disease and their specific protective mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Hu, Fu, Ye, Ao, Yan and Feng.)