The effect of inflammatory proteins on COVID-19 is mediated by blood metabolites: A Mendelian randomization study

Medicine, Journal Year: 2025, Volume and Issue: 104(11), P. e41852 - e41852

Published: March 14, 2025

Several studies have suggested that inflammatory proteins may be associated with Coronavirus disease 2019 (COVID-19). However, the specific causal relationship between 2 and whether blood metabolites act as mediators remains unclear. Therefore, purpose of present study is to investigate COVID-19 identify quantify role potential mediators. Two-sample Mendelian randomization (MR) 2-step mediated MR analyses were used relationships 91 proteins, 486 COVID-19. A random-effects inverse variance weighted (IVW) approach was primary analytical method, supplemented by medians, MR-Egger multivariate residual sums, outliers test hypotheses. Our results showed (interleukin-10 interleukin-18) positively risk, while 1 protein (PD-L1) negatively associated. Further validation performed using sensitivity analysis. The Betaine a mediator PD-L1 mediation ratio 15.92%. suggests genetic causality COVID-19, highlights mediating metabolite betaine, contributes deeper understanding mechanism action severe

Language: Английский

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Association between genetic prediction of 486 blood metabolites and the risk of idiopathic pulmonary fibrosis: A mendelian randomization study

Biomedical Reports, Journal Year: 2025, Volume and Issue: 22(3)

Published: Jan. 23, 2025

Metabolic disorders are a significant feature of fibrotic diseases. Nevertheless, the lack sufficient proof regarding cause‑and‑effect association between circulating metabolites and promotion or prevention idiopathic pulmonary fibrosis (IPF) persists. To assess causal IPF genetic proxies 486 blood metabolites, dual sample Mendelian randomization (MR) analysis was performed. Therefore, two‑sample MR technique genome‑wide study data were employed to serum IPF. produce primary outcomes, inverse variance weighted (IVW) applied, while stability dependability sensitivity using MR‑Egger Additionally, median, Cochran's Q‑test, Egger intercept test leave‑one‑out method used. The results present revealed total 21 in circulation that could affect risk (P_IVW<0.05). Among them, 10 compounds already known, namely cotinine [odds ratio (OR)=1.206; 95% confidence interval (CI), 1.002‑1.452; P=0.047], hypoxanthine (OR=0.225; CI, 0.056‑0.899; P=0.034), aspartyl phenylalanine (OR=4.309; 1.084‑17.131; P=0.038), acetyl‑carnitine (OR=5.767; 1.398‑23.789; P=0.015), 2‑aminobutyrate (OR=0.155; 0.033‑0.713; P=0.016), Docosapentaenoic acid (PubChem ID: 5497182; OR=0.214; 0.055‑0.833; P=0.026), octanoyl‑carnitine 177508; OR=3.398; 1.179‑9.794; P=0.023), alpha‑hydroxy‑isovalerate 857803‑94‑2; OR=0.324; 0.112‑0.931; P=0.036), 1,7‑dimethylurate 91611; OR=0.401; 0.172‑0.931; P=0.033) 1‑linoleoyl‑glycerophosphocholine 657272; OR=6.559; 1.060‑40.557; P=0.043). also identified 11 currently unknown chemical structures. Q‑test indicated there no heterogeneity, MR‑Egger's verified horizontal pleiotropy. retention one for plotting supported reliability analysis. Overall, current including with known composition which still awaiting determination. These findings provide novel insights further investigation mechanism underlying development

Language: Английский

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Genetic association of lipids and lipid-lowering drug target genes with breast cancer

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 17, 2025

Although several preclinical and epidemiological studies have shown that blood lipids lipid-lowering drugs can reduce the risk of breast cancer, this finding remains controversial. This study aimed to explore causal relationship between dyslipidemia,lipid-lowering drugs, cancer. We also evaluate potential impact drug targets on Data 431 lipid- lipid-related phenotypes were obtained from genome-wide association (GWAS), mendelian randomization (MR) analyses performed using two independent cancer datasets as endpoints. Genetic variants associated with genes encoding extracted Global Lipid Genetics Consortium. Expression quantitative trait loci data in relevant tissues used further validate reached significance combined bioinformatics approaches for molecular expression prognostic exploration. Further mediation mediators. In datasets, phosphatidylcholine (18:1_0:0 levels) was (discovery: odds ratio (OR) = 1.255 [95% confidence interval (CI) 1.120–1.406]; p 8.936 × 10–5, replication: OR 1.016 CI, 1.003–1.030]; 0.017), HMG- CoA reductase (HMGCR) inhibition genetically modeled a reduced 0.833 CI 0.752–0.923], 5.12 10–4; 0.975 0.960–0.990], 1.65 10–3). There significant MR correlation HMGCR whole (OR 1.11 1.01–1.22] 0.04). Bioinformatics analysis revealed higher than normal tissues, along poor overall survival relapse-free survival, multiple immune cell infiltration. Finally, showed inhibitors affected through different C-reactive protein levels. study, we found first time (18:1_0:0) levels are risk. part their action may be pathways other lipid-lowering, including modulation function reduction inflammation represented by

Language: Английский

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Association between systemic lupus erythematosus and cardiovascular health based on genetic data

Clinical Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: May 3, 2025

Language: Английский

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Mendelian randomization reveals the causal association between gout and hearing impairment in older adults

Medicine, Journal Year: 2024, Volume and Issue: 103(22), P. e38259 - e38259

Published: May 31, 2024

With the global aging trend escalating, holistic well-being of elderly has become a paramount concern within public health. Traditional observational studies often struggle with confounding factors and establishing causality, leaving relationship between age-related hearing loss (ARHL) gout largely unexplored. Employing bidirectional two-sample Mendelian randomization (MR) analysis, this investigation elucidated genetic underpinnings associated impairment, gout, urate levels IEU Open-GWAS database, thereby uncovering potential causal connections that underlie intricate interplay serum concentrations, auditory decline in geriatric demographic. In forward MR phase, cohort 30 single nucleotide polymorphisms was leveraged to dissect dynamics ARHL both concentrations. Conversely, reverse were posited as exposome delineate their impact on acuity, employing an array models for rigorous validation sensitivity scrutiny. statistically significant correlation discerned (P = .003, odds ratio 1.01, 95% confidence interval: 1.00-1.02), alongside notable association .031, 1.39, 1.03-1.88), intimating could potentially influence incidence revealed neither nor exerted degradation > .05), insinuating these might not predominantly contribute loss. Sensitivity analyses concurred inference. This study enriches comprehension health intricacies unveils influences suggests monitoring may play crucial role early identification management hyperuricemia, contributing comprehensive approach improving outcomes.

Language: Английский

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Revealing an association between HPV and systemic lupus erythematosus: A bidirectional two‐sample Mendelian randomization study

Skin Research and Technology, Journal Year: 2024, Volume and Issue: 30(8)

Published: Aug. 1, 2024

Abstract Background An increasing number of studies have focused on the association between Human papillomavirus (HPV) infection and systemic lupus erythematosus (SLE). However, current evidence is largely based retrospective studies, which are susceptible to confounding factors cannot establish causation. Methods A bidirectional two‐sample Mendelian randomization (MR) design was used evaluate causal relationship HPV SLE. Mononucleoside polymers (SNPS) with strong for genome‐wide (GWAS) were selected from exposure dataset as an instrumental variable (IV) this study. For MR Analysis results, MR‐Egger intercept P test, MR‐Presso global CochranQ test leave‐one sensitivity analysis. Results Based Analysis, study finally determined that there no HPV16 HPV18 Conclusions Possible regulation not significantly associated These findings provide new insights into underlying mechanisms SLE need be validated by further studies.

Language: Английский

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Betaine and I-LG may have a predictive value for ATB: A causal study in a large European population

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(7), P. e0306752 - e0306752

Published: July 5, 2024

Purpose To analyze the causal relationship between 486 human serum metabolites and active tuberculosis (ATB) in European population. Methods In this study, ATB was analyzed by integrating genome-wide association study (GWAS). The were used as exposure variable, three different GWAS databases population set outcome variables, single nucleotide polymorphisms instrumental variables for Mendelian Randomization. inverse variance weighting estimated causality, MR-Egger intercept to estimate horizontal pleiotropy, combined effects of also considered meta-analysis. Furthermore, web-based MetaboAnalyst 6.0 engaged enrichment pathway analysis, while R (version 4.3.2) software Review Manager 5.3 employed statistical analysis. Results A total 21, 17, 19 strongly associated with found after preliminary screening (P < 0.05). intersecting across these included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, oleoylcarnitine. Among them, betaine ( I 2 = 24%, P 0.27) 1-LG 0%, 0.62) showed lowest heterogeneity among databases. addition, metabolic pathways phosphatidylethanolamine biosynthesis 0.0068), methionine metabolism 0.0089), 0.0205) oxidation branched-chain fatty acids 0.0309) ATB. Conclusion Betaine may be biomarkers or auxiliary diagnostic tools They provide new guidance medical practice early diagnosis surveillance interfering biosynthesis, metabolism, acids, other pathways, it is helpful develop anti-tuberculosis drugs explore virulence pathogenesis at a deeper level, providing an effective reference future studies.

Language: Английский

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Male infertility risk and plasma lipidome: a Mendelian randomization study

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

Published: Aug. 14, 2024

Background In recent years, the decline in sperm quality men has become a global trend. There is close relationship between and pregnancy outcome. large body of literature supporting role plasma lipidome male infertility, while complex mechanisms them infertility are still less clear. Systematic study causal MI can help to provide new therapeutic ideas targets for infertility. Methods this study, we used two-sample Mendelian randomization analysis based on Genome-wide association studies pooled data 179 relationships We employed inverse variance weighted method as main assess causality exposure outcome, addition MR-Egger, Weighted median complementary methods, tests multiplicity heterogeneity. Results identified 13 comprising 4 types that were associated with Among these, 9 found be protective factors, risk factors. Notably, largest proportion these triglyceride types, Sphingomyelin (d40:1) exhibiting strongest Conclusion These findings contribute current better understanding perspectives underlying etiology well prevention treatment strategies. addition, clinical trial validation needed potential biomarkers.

Language: Английский

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The role of 1400 plasma metabolites in gastric cancer: A bidirectional Mendelian randomization study and metabolic pathway analysis

Medicine, Journal Year: 2024, Volume and Issue: 103(48), P. e40612 - e40612

Published: Nov. 29, 2024

While observational studies have illustrated correlations between plasma metabolites and gastric cancer (GC), the causal association 2 is still unclear. Our study aims to delineate bidirectional relationship GC find potential metabolic pathways. We undertook a 2-sample Mendelian randomization (MR) analysis investigate relationship, specificity, direction of 1400 GC. The GWAS data for was obtained from cohort 8299 European individuals. And GC’s FinnGen Consortium with 2384 individuals, catalog 1029 ancestry cases validation. Causal estimates were primarily calculated by inverse-variance weighted (IVW) method. To ensure robustness, we performed comprehensive sensitivity analyses assess heterogeneity address concerns regarding horizontal pleiotropy. validated forward another database implemented meta-analysis. Furthermore, conducted enrichment pathway these using MetaboAnalyst5.0/6.0 Kyoto Encyclopedia Genes Genomes. All statistical carried out R software. Metabolites like 2s, 3R-dihydroxybutyrate, 4-acetamidobutanoate, ferulic acid 4-sulfate methyl indole-3-acetate proven positively linked development Asparagine, glucose maltose ratio, glycohyocholate, Gulonate levels, linoleoyl ethanolamide Spermidine (N(1) + N(8))-acetylspermidine ratio be negatively associated Moreover, linoleic , histidine, glutamine, bilirubin Succinate proline found potentially our identified 18 significant pathways, including Arginine metabolism ( P < .009) Valine, leucine, isoleucine biosynthesis .031). findings offer evidence supporting casual relations multiple These may great future application biomarkers in screening clinical prevention strategies.

Language: Английский

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