Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 26, 2024

Background An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or immune cells act as mediators currently remains unclear. Methods We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential proteins, cells, NMOSD using data from genome-wide studies (GWAS). Five different methods for analyses were applied, with inverse variance-weighted (IVW) method being primary approach. Sensitivity further performed assess presence horizontal pleiotropy heterogeneity in results. Finally, two-step (MR) design was mediating effects cells. Results A notable relationship observed three (CSF-1, IL-24, TNFRSF9) genetically predicted NMOSD. Furthermore, two cell phenotypes, CD8 on naive CD8+ T Hematopoietic Stem Cell Absolute Count negatively positively associated NMOSD, respectively, although they did not appear function mediators. Conclusion Circulating are causally Immune do mediate pathway linking

Language: Английский

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Metabolic pathway and genetically causal links of 1,400 circulating metabolites on the risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage

Neuroscience, Journal Year: 2025, Volume and Issue: 568, P. 27 - 37

Published: Jan. 11, 2025

Language: Английский

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Genetic mapping of serum metabolome to chronic diseases among Han Chinese

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100743 - 100743

Published: Jan. 1, 2025

Language: Английский

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Multi-omic studies on the pathogenesis of Sepsis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 24, 2025

Language: Английский

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Metabolic Factors Mediate the Causal Effect of Physical Activity and Sedentary Behavior on Stroke and Its Subtypes: Evidence from Mendelian Randomization Study

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

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Identification of immune cells and circulating inflammatory factors associated with neurodevelopmental disorders by bidirectional Mendelian randomization and mediation analysis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 14, 2025

Abstract The roles of various immune cells and circulating inflammatory factors in neurodevelopmental disorders (NDDs) remain controversial. Therefore we employed a two-sample bidirectional Mendelian randomization mediation method to explore the causal relationships between cells, factors, NDDs. All data were originated from Genome-Wide Association Study (GWAS) datasets. We found significant positive relationship 13 autism spectrum disorder (ASD), including six CD8+ T one CD3+ cell, two CD20+ B CD38+ plasmacytoid DC. 9 showed with ASD: interleukins-7 (IL-7), interleukins-2 (IL-2), Interleukin-2 receptor subunit beta levels( IL-2β) interleukins-18 1 levels (IL-18-R1) negatively associated. In contrast, five positively associated, such as tumor necrosis factor-α (TNF-α). 14 exhibited attention deficit hyperactivity (ADHD). CD3 on naive CD8br CD4 activated Treg while four CD27-expressing associated ASD. Four CD40-expressing monocytes ADHD. 7 had ADHD: Fibroblast Growth Factor 23 (FGF-23), CD40L levels, Glial Cell Line-Derived Neurotrophic (GDNF), TNF-α more important among these. Mediation analysis identified 12 mediating relationships, three showing strong evidence: Natural killer cell 2B4 (19.9%), FGF-23 (11%), Eotaxin (− 5.95%). Strong existed Inflammatory mediated pathways

Language: Английский

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Exploring the effect of SGLT2 inhibitors on the risk of primary open-angle glaucoma using Mendelian randomization analysis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 22, 2025

This study aimed to evaluate the causal effect of sodium-glucose cotransporter protein 2 (SGLT2) inhibition on primary open-angle glaucoma (POAG) and explore potential mechanisms. A drug-targeted Mendelian randomization (MR) was conducted using genetic variation related SGLT2 inhibition, based gene expression glycated hemoglobin levels. Genetic summary statistics for POAG were obtained from FinnGen consortium a multi-ancestry genome-wide association study. Glaucomatous endophenotype data also incorporated. two-step MR analysis performed examine whether pathways obesity, blood pressure, lipid levels, oxidative stress, inflammation mediated between POAG. Genetically predicted associated with reduced risk (OR: 0.28; 95% CI: 0.12 0.63; P = 2.22 × 10- 3), confirmed in validation cohort. It decreased optic cup area, vertical cup-disc ratio, increased disc area. Mediation indicated that partly by diastolic pressure (4.8%). suggests is promising therapeutic target However, further large-scale randomized controlled trials are required confirm these findings.

Language: Английский

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The role of immune cell phenotypes and metabolites in the risk of ischemic stroke: a Mendelian randomization-based mediation analysis

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: May 6, 2025

Ischemic stroke (IS) occurs when a blood clot obstructs vessel supplying to the brain, leading brain tissue damage due insufficient oxygen and nutrients. The roles of immune cells metabolites in IS are increasingly recognized, yet their specific mechanisms remain unclear. This study conducted comprehensive statistical analysis explore relationships between cell phenotypes, metabolite levels, IS. We utilized methods such as inverse variance weighted (IVW), median, MR Egger ensure robust results. Sensitivity analyses were performed confirm absence significant heterogeneity or pleiotropy. identified several phenotypes significantly associated with Notably, IgD + CD24 AC showed positive association (OR = 1.045601, p 0.011562), while CD62L- HLA DR monocyte demonstrated negative 0.948673, 0.005415). Among metabolites, adenosine 5'-monophosphate (AMP) cysteine ratio was positively 1.083144, 0.000310), whereas xanthurenate levels negatively 0.926100, 0.001614). Mediation revealed mediating effect acetylcarnitine on relationship IS, an estimated mediation 0.00606 (p 0.036834077). Our highlights crucial suggesting potential novel therapeutic targets biomarkers. underscores complex interactions providing valuable insights for future research. These findings pave way further exploration pathophysiological strategies

Language: Английский

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Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: May 15, 2024

Background Hemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms the underlying biomolecular mechanisms its development. Circulating metabolites have closely associated with HS recent years. Therefore, we explored causal association between circulating metabolomes using Mendelian randomization (MR) analysis identified molecular effects. Methods We assessed relationship serum (CSMs) bidirectional two-sample MR method supplemented five ways: weighted median, Egger, simple mode, MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, MR-PRESSO served for sensitivity analyses. Steiger test reverse were used to estimate causality. Metabolic pathway analyses performed MetaboAnalyst 5.0, genetic effects by linkage disequilibrium score regression. Significant further synthesized meta-analysis, multivariate correct common confounders. Results finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40–0.96, P MVMR = 0.030), linoleate (18. 2n6) 0.20, 0.08–0.54, 0.001),1-eicosadienoylglycerophosphocholine* 2.21, 1.02–4.76, 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) 0.27, 0.09–0.77, 0.015) significant relation HS. Conclusion demonstrated associations hemorrhagic stroke. Monitoring, diagnosis, treatment might be valuable approach.

Language: Английский

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Causal impact of human blood metabolites and metabolic pathways on serum uric acid and gout: a mendelian randomization study

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Objective Hyperuricaemia and gout are common metabolic disorders. However, the causal relationships between blood metabolites serum urate levels, as well gout, remain unclear. A systematic evaluation of connections metabolites, hyperuricemia, could enhance early screening prevention hyperuricemia in clinical settings, providing novel insights approaches for treatment. Methods In this study, we employed a bidirectional two-sample Mendelian randomization analysis utilizing data from genome-wide association study involving 7,286 participants, encompassing 486 metabolites. Serum were sourced Chronic Kidney Disease Genetics consortium, including 288,649 participants 9,819 African American 753,994 European individuals gout. Initially, LDSC methodology was applied to identify with genetic relationship Subsequently, inverse-variance weighting primary method, series sensitivity pleiotropy analyses conducted assess robustness results. Results Following LDSC, 133 exhibited potential using weighting, 19 recognized potentially influencing levels IVW p-values corrected false discovery rate method. We find leucine (IVW P FDR = 0.00004), N-acetylornithine 0.0295), N1-methyl-3-pyridone-4-carboxamide succinyl carnitine 0.00004) identified significant risk factors elevated levels. Additionally, 1-oleoylglycerol 0.0007) may lead substantial increase Succinyl acceptable weak heterogeneity, results other remained robust after sensitivity, testing. an enrichment on followed by pathway revealing four pathways associated Conclusion The these offer perspective, new mechanistic into

Language: Английский

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