Renal Failure, Год журнала: 2024, Номер 46(2)
Опубликована: Окт. 18, 2024
Objectives The small GTPase Rac1 (RAC1) has been linked to podocyte disorders and steroid-sensitive nephrotic syndrome (SSNS). aim of this study was explore validate the potential causal association between circulating RAC1 SSNS.
Язык: Английский
Renal Failure, Год журнала: 2025, Номер 47(1)
Опубликована: Янв. 13, 2025
Identifying risk factors for disease onset and progression has been a core focus in nephrology research. Mendelian Randomization (MR) emerged as powerful genetic epidemiological approach, utilizing genome-wide association studies (GWAS) to establish causal relationships between modifiable kidney outcomes. MR uses variants instrumental variables infer exposures This method leverages the natural randomization of balance confounders, akin matched cohorts observational The rapid increase on poses challenges journals peer reviewers, especially clinicians unfamiliar with methodology. High-quality use strong, well-validated instruments clear biological relevance, thoroughly testing pleiotropy confounding using methods like MR-Egger. Sensitivity analyses, such MR-PRESSO, should ensure findings remain consistent across various assumptions. Effect sizes confidence intervals be reported discussed within established mechanisms. Additionally, limitations must transparently addressed, recommendations replication future studies, strengthen findings. article guides readers understanding application identifying high-quality helping peers avoid pitfalls while seizing new opportunities advancing
Язык: Английский
Процитировано
10
Biomedicines, Год журнала: 2025, Номер 13(3), С. 581 - 581
Опубликована: Фев. 25, 2025
Background: The current pharmacological treatments for Immunoglobulin A nephropathy (IgAN) demonstrate limited effectiveness and may cause serious side effects. This study aimed to explore novel potential drug targets IgAN. Methods: We utilized summarized data from a recent genome-wide association on IgAN, cis-expression quantitative trait loci druggable genes obtained the eQTLGen Consortium, DNA methylation derived GoDMC database. Two-sample Mendelian randomization (MR) analysis, Bayesian colocalization, mediation analysis through two-step MR approach were performed investigate their causal relationships. Results: colocalization analyses demonstrated that expression of HLA-DPA1 C4A was associated with an increased risk In contrast, TUBB, CYP21A2, C4B decreased Mediation revealed acted as mediator in relationship between three sites (cg01140143, cg08898074, cg12168509) mediated proportions 33.74% (95% CI 1.64–73.27), 41.67% 20.78–66.97), 50.34% 27.89–74.76), respectively. Conclusions: Several identified show associations IgAN be targeted development. Nevertheless, additional experimental validation is warranted clarify specific roles pathogenesis
Язык: Английский
Процитировано
0
Seminars in Nephrology, Год журнала: 2025, Номер unknown, С. 151567 - 151567
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Biological Research, Год журнала: 2025, Номер 58(1)
Опубликована: Апрель 5, 2025
Abstract Alzheimer's disease (AD) is a neurodegenerative disorder influenced by both genetic and environmental factors. Identifying therapeutic targets interventions remains challenging. This study utilized Mendelian Randomization (MR) to investigate causal relationships between plasma proteins, lifestyle factors, AD, along with virtual screening identify potential drug compounds. A two-sample MR analysis assessed associations identified through genome-wide association studies (GWAS), AD risk. Co-localization (CA) confirmed the overlap protein expression susceptibility loci, reverse ruled out causality. protein–protein interaction (PPI) network was constructed explore targets, followed small-molecule inhibitors for selected proteins. The found significant eight proteins five (GSTP1, BIN1, Siglec-3, SERPINF2, GRN) showing strong evidence of involvement in pathogenesis. Virtual six compounds as GSTP1 four BIN1. Furthermore, such dietary behaviors smoking cessation, indicated they may influence risk their effects on specific These findings offer novel insights into mechanisms underlying highlight combining targets. also suggests that modifications could alternative prevention treatment strategies AD. Future research should focus experimental validation further linking factors
Язык: Английский
Процитировано
0
Renal Failure, Год журнала: 2025, Номер 47(1)
Опубликована: Апрель 15, 2025
It has been proved that glucagon-like peptide-1 receptor (GLP1R) agonists have positive effects on renal outcomes in diabetic patients. However, it remains unknown whether GLP1R could provide similar protection against other kidney diseases. We performed two-sample Mendelian randomization (MR) analyses to determine the causal of multiple Exposure agonist was proxied by available cis-eQTLs for GLP1R. Primary included risk assessment nephropathy, IgA membranous nephrotic syndrome, chronic disease, acute glomerulonephritis, glomerulonephritis and calculus kidney/ureter. Type 2 diabetes body mass index were used as control. Two-stage network MR conducted assess mediation effect inflammatory proteins relationships between After meta-analyses both discovery validation cohorts, genetically found significantly associated with a decreased nephropathy (OR = 0.72, 95%CI 0.54-0.97, p 0.031) 0.58, 0.36-0.94, 0.027). revealed there an indirect through signaling lymphocytic activation molecule family member 1 (SLAMF1), mediated proportion 34.27% (95% CI, 1.47-67.03%, 0.041) total effect. The findings current study presented genetic proof potential protective development offering novel sight future mechanistic clinical applications.
Язык: Английский
Процитировано
0
Discover Oncology, Год журнала: 2025, Номер 16(1)
Опубликована: Май 2, 2025
The plasma proteins are an important source of therapeutic targets. This study aims to address the diagnostic and challenges bladder cancer (BC) by using Mendelian randomization (MR) with a large sample size from multiple centers identify which causally related pathogenesis BC. Followed merging nine protein datasets six studies, total 5538 three BC (ieu-b-4874, ukb-b-8193, FinnGen_R11_C3_ BLADDER_EXALL) were used perform proteome‑wide MR estimate contribution BC, separately. To ensure robustness results, Veen intersection operation on results revealed that 14 meaningful candidate pathogenic (ANKRD27, BIN1, FAHD1, IL17RB, MRPL21, PPT1, PSCA, SLC16A3, SLURP1, SPON2, TACSTD2, TMEM87B, YWHAB) obtain datasets. Then, we validated these through various methods, including meta-analysis, reverse MR, Bayesian co-localization analysis summary-data-based (SMR), divided into layers according validation confidence. We then performed single-cell transcriptome (Registration number: GSE222315), showed 13/14 expressed 12 differentially in at least one cell type. Finally, protein-protein interactions (PPI) druggability evaluation explore relationship between interaction markers existing drug Summarily, our research uncovered biomarkers linked risk, offering novel perspectives etiology potential targets for developing screening drugs
Язык: Английский
Процитировано
0
Journal of the American Society of Nephrology, Год журнала: 2024, Номер 35(8), С. 988 - 991
Опубликована: Июль 12, 2024
1Division of Nephrology, Department Medicine, Columbia University, New York, York 2Unit Genomic Variability and Complex Diseases, Medical Sciences, University Turin, Italy Correspondence: Dr. Simone Sanna-Cherchi, email: [email protected] See related article, "Circulating Proteins IgA Nephropathy: A Multiancestry Proteome-Wide Mendelian Randomization Study," on pages 1045–1057.
Язык: Английский
Процитировано
1
Renal Failure, Год журнала: 2024, Номер 46(2)
Опубликована: Окт. 18, 2024
Objectives The small GTPase Rac1 (RAC1) has been linked to podocyte disorders and steroid-sensitive nephrotic syndrome (SSNS). aim of this study was explore validate the potential causal association between circulating RAC1 SSNS.
Язык: Английский
Процитировано
0