Genetic Commonalities Between Metabolic Syndrome and Rheumatic Diseases Through Disease Interactome Modules

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(1)

Published: Jan. 1, 2025

ABSTRACT This study aims to elucidate the potential genetic commonalities between metabolic syndrome (MetS) and rheumatic diseases through a disease interactome network, according publicly available large‐scale genome‐wide association studies (GWAS). The analysis included linkage disequilibrium score regression analysis, cross trait meta‐analysis colocalisation identify common overlap. Using modular partitioning, network‐based two proteins in protein–protein interaction set was divided quantified. Clinical samples from public databases were used confirm mapped genes. Mendelian randomisation analyses conducted using instrumental variables for causal inference. MetS rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjogren's (SS) their primary module networks shared topological overlap correlation. Functional highlighted significance of these targets processes such as diverse array pathways involving glucose, lipids, energy, protein transport, inflammatory response, autophagy cytokine regulation, elucidating which intersects with diseases. Causal associations determined phenotypes persistence effects on remained evident even after adjusting alcohol consumption smoking. We have specific Several genes (e.g., PRRC2A, PSMB8, BAG6, GPSM3, PBX2, etc.) been identified molecular RA, AS, SLE SS, may serve treatments.

Language: Английский

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Association Between Rheumatoid Arthritis and Osteoporosis in Japanese Populations: A Mendelian Randomization Study

Arthritis & Rheumatology, Journal Year: 2023, Volume and Issue: 75(8), P. 1334 - 1343

Published: April 11, 2023

The positive association between rheumatoid arthritis (RA) and osteoporosis has been reported in previous observational studies, but the causal relationship remains unclear. This study was undertaken to investigate whether RA causally associated with Japanese populations using Mendelian randomization (MR) analyses.Publicly available summarized data from genome-wide studies (GWAS) on (4,199 cases 208,254 controls) (7,788 204,665 were obtained BioBank Japan. Eleven RA-related single-nucleotide polymorphisms (P < 5×10-8 ) selected as instrumental variables. We used inverse variance-weighted method primary calculate odds ratios (ORs) 95% confidence intervals (95% CIs). also MR-Egger's method, weighted median, mode determine robustness of main results. To partially test horizontal pleiotropy, we intercept pleiotropy residual sum outlier (MRPRESSO) test.Using showed that genetically predicted positively (OR 1.10, CI 1.06-1.14, P 0.001). robust when tested results 1.09, 1.03-1.16, = 0.023), median 1.04-1.15, 0.001), 1.08, 1.03-1.13, 0.012). Horizontal not detected 0.737) by or MRPRESSO test.Our show a potential osteoporosis. finding consistent different MR methods sensitivity analysis. Further are needed GWAS more details performed other East Asian/Japanese available.

Language: Английский

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Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 30, 2023

While targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific factors and CKD remains uncertain.Using a genome-wide association study of 41 serum cytokines from 8,293 Finnish individuals, we conducted bidirectional two-sample Mendelian randomization (MR) analysis. In addition, genetically predicted associations 5 phenotypes, including CKD, estimated glomerular filtration rate (eGFR), dialysis, rapid progression decline eGFR. Inverse variance weighting (IVW) served as primary MR method, while MR-Egger, weighted median, MR-pleiotropy residual sum outlier (MR-PRESSO) were utilized for sensitivity Cochrane's Q test heterogeneity. Leave-one-out method ensured stability results, Bonferroni correction assessed relationship strength.Seventeen associated with diverse renal outcomes. Among them, after test, higher tumor necrosis factor alpha levels decrease eGFR (OR = 1.064, 95% CI 1.028 - 1.103, P 0.001), interleukin-4 an increase (β 0.003, 0.001 0.005, 0.002), growth regulated oncogene (GROα) increased risk (OR=1.035, 1.012 1.058, 0.003). contrast, genetic susceptibility to was GROa, may lead stem cell factor. We did not find presence horizontal pleiotropy during analysis.We discovered causally related that contribute initiation at prediction level.

Language: Английский

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Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 18, 2023

The gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of with GI cancer has yet be fully established. We conducted this two-sample Mendelian randomization (MR) study reveal potential causal effect microbiota on cancer.Summary-level genetic data were derived from MiBioGen consortium and Dutch Microbiome Project. Summary statistics six cancers drawn United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), weighted-median (WM) methods used evaluate link between cancer. In addition, we performed sensitivity analyses reverse MR analyses.We identified associations 21 bacterial taxa (values p < 0.05 in all three methods). Among them, phylum Verrucomicrobia (OR: 0.17, 95% CI: 0.05-0.59, = 0.005) retained a strong negative association intrahepatic cholangiocarcinoma after Bonferroni correction, whereas order Bacillales 1.67, 1.23-2.26, 0.001) positive pancreatic Reverse indicated that was associated 17 microbial methods, among inverse colorectal family Clostridiaceae1 0.91, 0.86-0.96, by correction.Our implicates effects specific potentially providing new insights into prevention treatment through bacteria.

Language: Английский

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Association of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review

Metabolism and Target Organ Damage, Journal Year: 2024, Volume and Issue: 4(2)

Published: April 7, 2024

Chronic kidney disease (CKD) and nonalcoholic fatty liver (NAFLD), metabolic dysfunction-associated (MAFLD) steatotic (MASLD) account for substantial financial burden worldwide. These alarming features call enhanced efforts to prevent manage the development progression of CKD. Accumulating evidence supporting a causal role NAFLD/MAFLD/MASLD-in CKD opens new horizons achieve this aim. Recent epidemiological studies meta-analyses exploring association NAFLD/MAFLD/MASLD with characteristics associated odds incident are discussed. The involved pathomechanisms, including common soil hypothesis, genetics, gut dysbiosis, portal hypertension, examined in detail. Finally, lifestyle changes (diet physical exercise), direct manipulation microbiota, drug approaches involving statins, renin-angiotensin-aldosterone system inhibitors, GLP-1 Receptor Agonists, Sodium-glucose cotransporter-2, pemafibrate, vonafexor within context prevention management among those NAFLD/MAFLD/MASLD. evolving nomenclature may generate confusion practicing clinicians investigators. However, comparative investigating pros contra different nomenclatures identify most useful definitions strategies identify, prevent, halt onset

Language: Английский

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The association between gut microbiome and PCOS: evidence from meta-analysis and two-sample mendelian randomization

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 24, 2023

Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) polycystic ovary syndrome (PCOS), however, causality direction of microbiome PCOS remains to be established. We conducted comprehensive search four databases-PubMed, Cochrane Library, Web Science, Embase up until June 1, 2023, subjected results meta-analysis. In this study, bidirectional two-sample Mendelian randomization (MR) analysis was employed investigate impact microbiota on (PCOS). The genome-wide association study (GWAS) data for comprised 113,238 samples, while GWAS were derived MiBioGen consortium, encompassing total sample size 18,340 individuals. As largest dataset its kind, represents most meta-analysis concerning composition date. Single nucleotide polymorphisms (SNPs) selected as instrumental variables at various taxonomic levels, including Phylum, Class, Order, Family, Genus. causal associations exposures outcomes assessed using established MR methods. To correct multiple testing, false discovery rate (FDR) method applied. reliability potential biases evaluated through sensitivity F-statistics. incorporated 20 that met criteria, revealing close specific species. per our analysis, we identified six At genus level, Actinomyces (ORIVW = 1.369, FDR 0.040), Streptococcus 1.548, 0.027), Ruminococcaceae UCG-005 1.488, 0.028) risk factors PCOS. Conversely, Candidatus Soleaferrea 0.723, Dorea 0.580, 0.032), UCG-011 0.732, 0.030) found protective against Furthermore, MR-PRESSO global test MR-Egger regression not affected by horizontal pleiotropy (p > 0.05). Finally, leave-one-out corroborated robustness findings. Both indicates there is relationship PCOS, which may contribute providing novel insights development new preventive therapeutic strategies

Language: Английский

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Oral Cardiac Drug–Gut Microbiota Interaction in Chronic Heart Failure Patients: An Emerging Association

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1716 - 1716

Published: Jan. 31, 2024

Regardless of the currently proposed best medical treatment for heart failure patients, morbidity and mortality rates remain high. This is due to several reasons, including interaction between oral cardiac drug administration gut microbiota. The relation drugs (especially antibiotics) microbiota well established, but it also known that more than 24% non-antibiotic affect microbiota, altering microbe's environment its metabolic products. Heart lies mainly in blockage neuro-humoral hyper-activation. There debate as whether heart-failure-specific can totally block this hyper-activation, or so-called intestinal dysbiosis commonly observed group patients their action. Although there are reports indicating a strong drug-gut interplay, little about chronic failure. In review, we review contemporary data on topic infancy. We aim produce scientific thoughts questions provide reasoning further clinical investigation.

Language: Английский

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Association between sleep-related phenotypes and gut microbiota: a two-sample bidirectional Mendelian randomization study

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

Published: Feb. 2, 2024

Background An increasing body of evidence suggests a profound interrelation between the microbiome and sleep-related concerns. Nevertheless, current observational studies can merely establish their correlation, leaving causality unexplored. Study objectives To ascertain whether specific gut microbiota are causally linked to seven characteristics propose potential strategies for insomnia prevention. Methods The study employed an extensive dataset genetic variations from MiBioGen alliance, encompassing 18,340 individuals. Taxonomic classification was conducted, identifying 131 genera 196 bacterial taxa analysis. Sleep-related phenotype (SRP) data were sourced IEU OpenGWAS project, covering traits such as insomnia, chronotype, snoring. Instrumental variables (IVs) selected based on criteria, including locus-wide significance, linkage disequilibrium calculations, allele frequency thresholds. Statistical methods explore causal relationships, inverse variance weighted (IVW), MR-Egger, median, Mode. Sensitivity analyses, pleiotropy assessments, Bonferroni corrections ensured result validity. Reverse analysis adherence STROBE-MR guidelines conducted bolster study’s rigor. Results Bidirectional Mendelian randomization (MR) reveals causative interplay phenotypes. Notably, outcomes rigorously Bonferroni-corrected examination illuminate correlations amid precise compositions intestinal slumber-associated parameters. Elevated abundance within taxonomic ranks class Negativicutes order Selenomonadales markedly associated with heightened susceptibility severe (OR = 1.03, 95% CI: 1.02–1.05, p 0.0001). Conversely, augmented representation phylum Lentisphaerae stands in concord protracted sleep duration 1.02, 1.01–1.04, 0.0005). Furthermore, exposure genus Senegalimassilia exhibits ameliorate manifestation snoring symptoms 0.98, 0.96–0.99, Conclusion This has unveiled relationship SRPs, bestowing significant latent value upon future endeavors both foundational research clinical therapy.

Language: Английский

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Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization analysis

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

Published: Feb. 8, 2024

Background Despite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship them remains unclear. Methods Gut data were obtained from MiBioGen collaboration, SpA genome-wide study (GWAS) summary FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, mode). Pleiotropy heterogeneity also assessed. Reverse was used to detect reverse relationships. Results identified 23 links specific taxa levels. Of these, 22 displayed nominal associations, only one demonstrated robust connection. Actinobacteria id.419 increased risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29–2.69); p 8.63 E −04). The family Rikenellaceae id.967 associated reduced both AS (OR 0.66 CI: 0.47–0.93); 1.81 −02) psoriatic arthritis 0.70 0.50–0.97); 3.00 −02). Bacillales id.1674 1.23 1.00–1.51); 4.94 decreased enteropathic 0.56 0.35–0.88); 1.14 Directional pleiotropy, or heterogeneity, not observed. No associations observed diseases microbiota. Conclusion Our suggested genetic-level SpA, providing insights into underlying mechanisms behind development mediated by

Language: Английский

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Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: Results from a bidirectional two-sample two-step Mendelian randomisation

Gene, Journal Year: 2024, Volume and Issue: 911, P. 148320 - 148320

Published: March 5, 2024

Non-Hodgkin's lymphoma incidence rates vary between European and Asian populations. The reasons remain unclear. This two-sample two-step Mendelian randomisation (MR) study aimed to investigate the causal relationship anthropometric indicators (AIs) diffuse large B-cell (DLBCL) follicular (FL) possible mediating role of basal metabolic rate (BMR) in Europe.

Language: Английский

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