ArticleEuropean journal of epidemiology2021
Mendelian randomisation for mediation analysis: current methods and challenges for implementation.
Article in European journal of epidemiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06666647 (Ambulance and Helicopter Response Times in Danish Emergency Medical Services), which is not on this map. Cited by 778 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Ambulance and Helicopter Response Times in Danish Emergency Medical Services: Protocol for an Epidemiological Study. The AHRTEMIS Study
Who cites it
778 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- The mediating effects of plasma proteome on the association between selenium and systemic lupus erythematosus.Clinical rheumatology · 2026Pooled it
- Glucagon-like peptide-1 receptor agonists, inflammation, and kidney diseases: evidence from Mendelian randomization.Renal failure · 2025Pooled it
- The mechanisms of kidney-lung interactions in chronic kidney disease-associated pulmonary diseases: A two-sample Mendelian randomization study.Renal failure · 2025Pooled it
- Insulin Resistance and Blood Pressure Control on Cognitive Outcomes.Hypertension (Dallas, Tex. : 1979) · 2026Trial
- Causal links between gut microbiota, plasma metabolites, and insomnia: Insights from Mendelian randomization.Dialogues in clinical neuroscience · 2026Article
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- Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses.Biochemical genetics · 2026Article
- Genetic evidence supports a cortical neuroprotective role of GLP-1 receptor activation in Alzheimer's disease: A drug-target Mendelian randomization study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- How gut microbiome and blood metabolites drive ossification of the posterior longitudinal ligament of the spine: a genome-wide association study based on the East Asian population.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- Plasma VGF as a Predictive Biomarker for Early Acute Kidney Injury in Critically Ill Elderly Patients:Saudi medical journal · 2026Article
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- Genetically predicted ZDHHC8 expression and osteoporosis risk: A two-sample Mendelian randomization and metabolite mediation study.Medicine · 2026Article
- Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease.Nature cardiovascular research · 2026Article
- Exploring the shared genetic architecture and causal relationship between childhood maltreatment and psychiatric disorders.Molecular psychiatry · 2026Article
- Article
- Genetically supported targets and drug repurposing for sleep disorders: a Mendelian randomization systematic study.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
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- Integrative plasma proteomic network analysis identifies physical activity-associated protein modules potentially mediating type 2 diabetes risk.Cardiovascular diabetology · 2026Article
- Mobile Phone Call Duration and Cardiovascular Outcomes: Prospective and Genetic Evidence on a Potential Depression-Related Pathway.Bioengineering (Basel, Switzerland) · 2026Article
- The role of ferroptosis in juvenile idiopathic arthritis: Causal inference and mediation by immune phenotypes.Medicine · 2026Article
718 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Mediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.