Genetic insights into the roles of fatty acids and gut microbiota in osteoarthritis: A Mendelian randomization study DOI Creative Commons
Yilei Lu, Zekun Zhou,

Ding Pan

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(49), P. e40674 - e40674

Published: Dec. 6, 2024

Traditional observational studies have shown that fatty acids and gut microbiota are crucial in osteoarthritis (OA) progression, but their findings often conflicting due to biases, confounding factors, measurement errors. We conducted a two-sample Mendelian randomization analysis using genome-wide association study data on from 136,016 individuals, the 7738 314,870 individuals. Elevated levels of total (odds ratio [OR]: 0.92; 95% CI 0.84–1.00; P = .039), saturated (OR: 0.91; 0.84–0.99; .034), linoleic acid 0.85–1.00; .040) were associated with reduced OA risk. In terms microbiota, Bifidobacterium adolescentis 0.89; 0.80–1.00; .048) Escherichia 0.90; 0.81–1.00; .042) demonstrated protective roles against OA. Conversely, Oscillibacter 1.16; 1.00–1.34; .043), Bilophila 1.28; 1.07–1.54; .007), Erysipelotrichaceae 1.08; 1.00–1.16; .044), within Desulfovibrionaceae family 1.19; 1.04–1.36; .012) an increased risk The indicate modulating dietary factors can independently reduce progression OA, potentially improving quality life health management aging populations.

Language: Английский

Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study DOI Creative Commons
Jingyi Tang,

Shengke Zhang,

Lai Jiang

et al.

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(13), P. 4219 - 4231

Published: Jan. 1, 2024

Hepatocellular carcinoma (HCC), the predominant malignancy of digestive tract, ranks as third most common cause cancer-related mortality globally, significantly impeding human health and lifespan. Emerging immunotherapeutic approaches have ignited fresh optimism for patient outcomes. This investigation probes link between 731 immune cell phenotypes HCC through Mendelian Randomization single-cell sequencing, aiming to unearth viable drug targets dissect HCC's etiology.

Language: Английский

Citations

12
Plasma proteome and incident myocardial infarction: sex-specific differences DOI Creative Commons
Olga E. Titova, Shuai Yuan, Liisa Byberg

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(43), P. 4647 - 4657

Published: Sept. 23, 2024

Abstract Background and aims Few population-based cohort studies, including both men women, have explored circulating proteins associated with incident myocardial infarction (MI). This study investigated the relationships between cardiometabolic-related MI risk using cohort-based Mendelian randomization (MR) analyses potential sex-specific differences. Methods The discovery included 11 751 Swedish adults (55–93 years). Data on 259 assessed Olink proximity extension assays, biochemical, questionnaire-based information were used. Participants followed up for death over 8 years through linkage to registers. Replication conducted UK Biobank sample (n = 51 613). In MR analyses, index cis-genetic variants strongly related used as instrumental variables. Genetic association summary statistic data obtained from CARDIoGRAMplusC4D consortium FinnGen. Results Forty-five in replication samples following adjustment confounders multiple testing. secondary analysis, 13 of protein associations sex-specific, most identified among women. genetically predicted higher levels renin, follistatin, retinoic acid receptor responder 2 linked an increased MI. Tissue factor pathway inhibitor, tumor necrosis receptors 1 2, placenta growth had inverse Conclusions new confirmed previously established and, first time, suggested patterns protein-MI associations.

Language: Английский

Citations

11
Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development DOI Creative Commons
Haobo Li, Zhu Zhang, Yuting Qiu

et al.

Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 68(12), P. 805 - 812

Published: Aug. 3, 2023

Abstract Genome-wide association studies (GWAS) have identified numerous risk loci for venous thromboembolism (VTE), but it is challenging to decipher the underlying mechanisms. We employed an integrative analytical pipeline transform genetic associations identify novel plasma proteins VTE. Proteome-wide (PWAS) were determined by functional summary-based imputation leveraging data from a genome-wide analysis (14,429 VTE patients, 267,037 controls), blood proteomes (1348 cases), followed Mendelian randomization, Bayesian colocalization, protein-protein interaction, and pathway enrichment analysis. Twenty genetically regulated circulating protein abundances (F2, F11, ABO, PLCG2, LRP4, PLEK, KLKB1, PROC, KNG1, THBS2, SERPINA1, RARRES2, CEL, GP6, SERPINE2, SERPINA10, OBP2B, EFEMP1, F5, MSR1) associated with Of these 13 demonstrated randomized correlations. Six SERPINE2) had strong support in colocalization Utilizing multidimensional data, this study suggests SERPINE2 as compelling that may provide key hints future research possible diagnostic therapeutic targets

Language: Английский

Citations

21
Proteomic insights into modifiable risk of venous thromboembolism and cardiovascular comorbidities DOI Creative Commons
Shuai Yuan,

Fengzhe Xu,

Han Zhang

et al.

Journal of Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 22(3), P. 738 - 748

Published: Nov. 27, 2023

Language: Английский

Citations

15
Potential Functions and Causal Associations of GNLY in Primary Open-Angle Glaucoma: Integration of Blood-Derived Proteome, Transcriptome, and Experimental Verification DOI Creative Commons
D.Y. Wang,

Yanyu Pu,

Xi Gao

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 367 - 380

Published: Jan. 1, 2025

Purpose: Genome-wide association studies (GWAS) have identified multiple genetic loci associated with primary open-angle glaucoma (POAG). However, the mechanisms by which these contribute to POAG progression remain unclear. This study aimed identify potential causative genes involved in development of POAG. Methods: We utilized multi-dimensional high-throughput data, integrating proteome-wide study(PWAS), transcriptome-wide (TWAS), and summary data-based Mendelian randomization (SMR) analysis. approach enabled identification influencing risk affecting gene expression protein concentrations bloodstream. The key was validated through enzyme-linked immunosorbent assay (ELISA) Results: PWAS 86 altered blood levels patients. Of these, eight (SFTPD, CSK, COL18A1, TCN2, GZMK, RAB2A, TEK, GNLY) were as likely for ( P SMR < 0.05). TWAS revealed that GNLY significantly at level. GNLY-interacting found play roles immune dysregulation, inflammation, apoptosis. Clinical cell-based validation confirmed reduced groups. Conclusion: reveals a significant therapeutic target managing glaucoma. Keywords: glaucoma, GNLY, PWAS,

Language: Английский

Citations

0
The causal impact of gut microbiota and metabolites on myopia and pathological myopia: a mediation Mendelian randomization study DOI Creative Commons
Jingwen Hui, Kexin Tang,

Yuejun Zhou

et al.

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

Published: April 15, 2025

Myopia, a major cause of irreversible visual impairment globally, is projected to affect about 25% the world's population by 2025. Myopia progresses through childhood and adolescence, necessitating frequent prescription updates. While genetic environmental factors are well-established contributors myopia, emerging evidence suggests significant role gut microbiota (GM) in its development, mainly metabolic interactions. This study utilized Mendelian Randomization (MR) approach investigate causal relationships between GM, metabolites, myopia pathological (PM) progression. Using variants as instrumental variables, we analyzed data from extensive genome-wide association studies (GWAS) assess impacts 473 GM taxa 233 metabolites on risks. Our MR analysis identified specific with relationship PM. Notably, lipid were found mediate effects suggesting biochemical pathway that could influence ocular development We also observed mediation effects, indicating might serve therapeutic targets modulate The findings highlight potential novel for preventing or managing myopia. underscores importance further research into gut-metabolite-eye axis develop targeted interventions based modifying diet, probiotics, other means. Future should aim elucidate involved their roles health, potentially offering new avenues treatment.

Language: Английский

Citations

0
The Plasma Proteome and Risk of Future Venous Thromboembolism—Results from the HUNT Study in Thrombosis and Haemostasis DOI
Drew A. Birrenkott, Christopher Kabrhel

Thrombosis and Haemostasis, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Language: Английский

Citations

0
Stress-Induced Hypercoagulability: Insights from Epidemiological and Mechanistic Studies, and Clinical Integration DOI
Roland von Känel

Seminars in Thrombosis and Hemostasis, Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

Abstract By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced hypercoagulability in clinical medicine. In particular, numerous prospective cohort studies indicate that stress hemostatic factors a hypercoagulable state are associated with increased incident risk poor prognosis for atherosclerotic cardiovascular disease venous thromboembolism. Mendelian randomization suggest these associations partially causal. The review synthesizes extensive research on link between acute chronic hypercoagulability, outlining potential pathway to thrombosis risk. Consistent allostatic load concept, initially adaptive, can turn maladaptive under or excessive stress, leading arterial thrombotic events. Individuals predisposing factors, including atherosclerosis, thrombophilia, immobilization, may exhibit an during stress. Contextual sociodemographic characteristics, experience, coping resources additionally modulate extent hypercoagulability. Research into neuroendocrine, cellular, molecular bases reveals how influences platelet activation coagulation fibrinolysis. sympathetic nervous system hypothalamic–pituitary–adrenal axis, along vagal withdrawal, effects catecholamines, cortisol, vasopressin, central mechanisms involved. Hemoconcentration, inflammation, endothelial dysfunction, thrombopoiesis contribute Further is needed prove causal This includes exploring its implications prevention management diseases stressed individuals, focus developing effective psychosocial pharmacological interventions.

Language: Английский

Citations

3
Deciphering the genetic architecture of atrial fibrillation offers insights into disease prediction, pathophysiology and downstream sequelae DOI Creative Commons
Shuai Yuan, Yuying Li, Lijuan Wang

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 25, 2023

Abstract Aims The study aimed to discover novel genetic loci for atrial fibrillation (AF), explore the shared etiologies between AF and other cardiovascular cardiometabolic traits, uncover pathogenesis using Mendelian randomization analysis. Methods results We conducted a genome-wide association meta-analysis including 109,787 cases 1,165,920 controls of European ancestry identified 215 loci, among which 91 were novel. performed Genomic Structural Equation Modeling analysis four comorbidities (coronary artery disease, ischemic stroke, heart failure, vneous thromboembolism) found 189 across these diseases as well universal locus by atherosclerotic outcomes (i.e., rs1537373 near CDKN2B ). Three (rs10740129 JMJD1C , rs2370982 NRXN3 rs9931494 FTO ) associated with traits. A polygenic risk score derived from this was (odds ratio 2.36, 95% confidence interval 2.31-2.41 per standard deviation increase) in UK biobank. This score, combined age, sex, basic clinical features, predicted (AUC 0.784, CI 0.781-0.787) Europeans. Phenome-wide many AF-related circulatory, endocrine, respiratory systems. multi-omic analyses associations blood lipids pressure, diabetes, insomnia, obesity, short sleep, smoking, 27 proteins, one gut microbe ( genus.Catenibacterium ), 11 metabolites AF. Conclusions trans-omic provides insights into disease prediction, pathophysiology downstream sequelae.

Language: Английский

Citations

5
Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure DOI Creative Commons
Yao Yao, Yanli Li,

Qinchun Jin

et al.

Cardiovascular Therapeutics, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Insufficient data exist regarding the investigation of impact novel oral anticoagulants (NOACs) on coagulation activation biomarkers in context left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate changes presence between different antithrombotic strategies following LAAC. A total 120 nonvalvular fibrillation patients intolerant long-term anticoagulants, who underwent successful WATCHMAN implantation, were enrolled (rivaroxaban,

Language: Английский

Citations

1