A practical guide for nephrologist peer reviewers: understanding and appraising Mendelian randomization studies

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

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Causal Relationship Between Emotional Disorders and Thyroid Disorders: A Bidirectional Two‐Sample Mendelian Randomization Study

Brain and Behavior, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

ABSTRACT Introduction The interplay between emotional disorders and thyroid has been subject to numerous observational studies, which have consistently reported associations but failed establish clear causal links due the multifactorial etiology influences. We conducted a bidirectional two‐sample Mendelian randomization (MR) analysis explore genetic association disorders. Methods employed several methods, including inverse‐variance weighted (IVW), median, mode, MR Egger regression. Additionally, sensitivity analyses were using MR‐Egger, Pleiotropy Residual Sum Outlier (MR‐PRESSO), Cochran's Q, leave‐one‐out methods. Results IVW results showed negative relationships hypothyroidism, toxic single nodules in thyrotoxicosis, hyperthyroidism/toxicity. there was positive relationship anxiety hypothyroidism. of reverse estimates revealed autoimmune thyroiditis, recurrent or chronic depression. hyperthyroidism/toxicity bipolar disorder. Conclusion This study preliminarily reveals complex, disorders, particularly highlighting role dysfunction development certain vice versa.

Язык: Английский

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Causal Association Between Skin Microbiota and Malignant Melanoma: Genetic Insights From Mendelian Randomization

Clinical Cosmetic and Investigational Dermatology, Год журнала: 2025, Номер Volume 18, С. 303 - 310

Опубликована: Янв. 1, 2025

Malignant melanoma (MM) is an extremely aggressive type of skin cancer that represents a major risk to human health. Earlier observational research has indicated microbiota could play role in the development and advancement MM. Nevertheless, causal link between MM still unclear. Utilizing data from genome-wide association studies (GWAS) conducted on European cohort, we applied Mendelian randomization (MR) evaluate The analysis involved various MR methodologies, including inverse variance weighting (IVW), MR-Egger regression, weighted median, mode simple mode. Furthermore, performed sensitivity employing intercept test MR-Egger, Cochran's Q test, MR-PRESSO approach, leave-one-out method. By conducting KORA FF4 identified several microbiotas (ASV003 [Staphylococcus (unc).], ASV016 [Enhydrobacter ASV021 [Micrococcus (unc).]) related with elevated Conversely, genus: Finegoldia class: Alphaproteobacteria were shown inhibit occurrence Additionally, PopGen cohort revealed (unc).] family: Moraxellaceae as possible factors for Our offers new insights into connection MM, indicating might affect onset Therefore, focusing be valuable strategy prevention, identification, management

Язык: Английский

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Causal associations between childhood obesity and delayed puberty or height: a bidirectional two-sample Mendelian randomization study

Journal of Pediatric Endocrinology and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Abstract Objectives Childhood obesity is thought to influence pubertal development, according observational studies. However, the exact causal relationship remains unclear due complexity of factors affecting development. Methods To explore association between exposure (childhood obesity) and outcome (delayed puberty, height), we utilized various methods, including inverse-variance weighted (IVW), median, mode, MR Egger regression. Additionally, sensitivity analyses were conducted using MR-Egger, MR-PRESSO, Cochran’s Q, leave-one-out techniques ensure robustness results. reverse analysis was potential causation. Results The IVW revealed no significant genetic link childhood delayed puberty or height (all P>0.05). In analysis, had a with (OR=0.85, 95 % CI=0.76–0.96). Q test highlighted heterogeneity in results concerning (p<0.05). But MR-Egger intercept MR-PRESSO confirmed impact pleiotropic bias, supported by analysis. Conclusions Our study found height. causally associated obesity. Future research should utilize advanced analytical methods better understand determinants

Язык: Английский

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Smoking may be a risk factor for carpal tunnel syndrome: Insights from Mendelian randomization analysis

Tobacco Induced Diseases, Год журнала: 2025, Номер 23(January), С. 1 - 7

Опубликована: Янв. 30, 2025

It is currently uncertain whether smoking a risk factor for carpal tunnel syndrome (CTS). This study aims to elucidate association between and CTS using Mendelian randomization (MR) analysis. was secondary analysis of publicly available GWAS data, four phenotypes (smoking initiation, status, lifetime smoking, never smoking) as exposures, two datasets (discovery validation sets) outcomes MR The discovery set (n=480201) used explore the causal relationship CTS, while (n=385304) confirm results. effects on were assessed inverse variance weighted (IVW), MR-Egger, median methods. Cochran's Q test detect heterogeneity, MREgger pleiotropy. Finally, meta-analysis performed IVW results from both sets. showed that in sets, are factors CTS. summary follows: initiation (OR=1.17; 95% CI: 1.08-1.27, p<0.001), status (OR=1.87; 1.56-2.24, (OR=2.46; 2.03-3.00, p<0.001). Conversely, protective against with result being: OR=0.55; 0.42-0.71, p<0.001. Based genetic evidence, may be Further clinical trials needed this relationship.

Язык: Английский

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Mediating Mendelian randomization in the proteome identified potential drug targets for obesity-related allergic asthma

Hereditas, Год журнала: 2025, Номер 162(1)

Опубликована: Фев. 1, 2025

With the development of economy, number obese patients has been increasing annually worldwide. The proportion asthma associated with obesity is also gradually rising. However, pathogenesis obesity-related remains incompletely understood, and conventional pharmacological treatments generally show limited efficacy. This study aims to explore causal relationship between allergic asthma, elucidate identify plasma proteins involved in its development, providing new insights for clinical interventions. In this study, we employed a two-step approach mediation Mendelian randomization (MR) analysis, utilizing stringent selection criteria instrumental variables (IVs). was used assess impact on validate identified as mediating factors. We further explored functions enriched pathways using Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses. Finally, conducted drug-targeted MR analysis evaluate potential each mediator drug target gene. If significant heterogeneity remained among IVs, applied weighted median method primary analytical tool. Otherwise, utilized inverse variance (IVW) main approach. Additionally, various sensitivity analyses statistical tests illustrate robustness observed associations. research findings indicate asthma. Plasma such TPST1, ROR1, DAPK1 mediate relationship, TPST1 accounting over 10% effect. GO KEGG that genes corresponding these are primarily related responses stimuli, carbohydrate synthesis metabolism, regulation certain protein activities, synaptic connections. suggests SIGLEC12, BOLA1, HOMER2, all have be genes. defined by BMI may promote influencing expression DAPK1. Furthermore, some proteins, including could potentially serve therapeutic targets treating patients. needed their mechanisms underlying effects. Not applicable.

Язык: Английский

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Mapping the exposome of mental health: exposome-wide association study of mental health outcomes among UK Biobank participants

Psychological Medicine, Год журнала: 2025, Номер 55

Опубликована: Янв. 1, 2025

Abstract Background Dissecting the exposome linked to mental health outcomes can help identify potentially modifiable targets improve well-being. However, multiplicity of exposures and complexity phenotypes pose a challenge that requires data-driven approaches. Methods Guided by our previous systematic approach, we conducted hypothesis-free exposome-wide analyses factors associated with 7 psychiatric diagnostic domains 19 symptom dimensions in 157,298 participants from UK Biobank Mental Health Survey. After quality control, 294 environmental, lifestyle, behavioral, economic variables were included. An Exposome-Wide Association Study was per outcome two equally split datasets. Variables each then tested multivariable model. Results Across all dimensions, top three childhood adversities traumatic events. Cannabis use common disorders (depressive, anxiety, psychotic, bipolar manic disorders), ORs ranging 1.10 1.79 models. Additionally, differential associations identified between specific outcomes—such as neurodevelopmental disorders, eating self-harm behaviors—and exposures, including early life experiences (being adopted), lifestyle (time spent using computers), dietary habits (vegetarian diet). Conclusions This comprehensive mapping revealed several factors, particularly those previously well-studied shared across phenotypes, providing further support for transdiagnostic pathoetiology. Our findings also showed distinct relations might exist. Continued research through multimodal mechanistic studies guided framework is required better inform public policies.

Язык: Английский

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Genetically Elevated Selenoprotein S Levels and Risk of Stroke: A Two-Sample Mendelian Randomization Analysis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1652 - 1652

Опубликована: Фев. 14, 2025

Selenoprotein S (SELENOS), one of the carrier proteins dietary selenium (Se), is a key regulator inflammation, oxidative stress, and endoplasmic reticulum (ER) all which are implicated in pathogenesis stroke. However, causality between SELENOS stroke risk remains poorly understood. This study aimed to explore association genetically determined plasma levels all-cause stroke, ischemic intracerebral hemorrhage (ICH) using two-sample Mendelian randomization (MR) approach. We analyzed data from three large-scale Genome-Wide Association Study (GWAS) meta-analyses individuals European descent. The fixed-effect inverse-variance weighted (IVW) model analysis revealed that elevated were associated with an increased ICH. Sensitivity analyses showed no evidence pleiotropy or heterogeneity, leave-one-out confirmed robustness our results. Here, we show causally linked risk. Although effect sizes modest, these findings suggest may play role pathogenesis, emphasizing need for further mechanistic functional studies. Finally, shed light on importance tailored Se intake management context prevention.

Язык: Английский

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Ankylosing spondylitis and the genetic correlation of extra-articular manifestations: Evidence from bidirectional Mendelian randomization and Bayesian colocalization

Medicine, Год журнала: 2025, Номер 104(7), С. e41388 - e41388

Опубликована: Фев. 14, 2025

Spondyloarthritis (SpA) encompasses a group of inflammatory joint disorders affecting the spine and joints, including ankylosing spondylitis nonradiographic axial SpA, exhibiting diverse extra-articular manifestations. Genetic factors, beyond human leukocyte antigen B27, play significant role in SpA development. Leveraging advanced statistical methods, this study explores bidirectional Mendelian randomization (MR) Bayesian colocalization to unravel genetic links between its Positive MR analysis indicates causal relationships various conditions. Leave-one-out suggests that these effects are not driven by individual single-nucleotide polymorphisms. In reverse MR, potential explored, revealing uveitis, bowel disease, ulcerative colitis as candidates. Colocalization analysis, unfortunately, does identify shared foundations. conclusion, seronegative spinal arthritis may lead myocarditis, atrioventricular block, bronchiectasis, Crohn coccygeal plexus syndrome, while there is 2-way relationship with colitis.

Язык: Английский

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Unveiling causal relationships between tobacco use phenotypes and neuroimaging: Insights from bidirectional Mendelian randomization and bibliometric analysis

Brain Research Bulletin, Год журнала: 2025, Номер 223, С. 111277 - 111277

Опубликована: Фев. 26, 2025

Язык: Английский

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