ArticleObesity (Silver Spring, Md.)2023
Challenges in undertaking nonlinear Mendelian randomization.
Article in Obesity (Silver Spring, Md.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Application of Mendelian randomized research method in oncology research: bibliometric analysis.Frontiers in oncology · 2024Pooled it
- Using Negative Control Outcomes to Detect Selection Bias in Mendelian Randomization Studies.Statistics in medicine · 2026Article
- Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study.Journal of the American College of Cardiology · 2026Article
- Genome-wide association study of positive and negative affect reveals shared genetic architecture and a potential causal relationship with cognition.Scientific reports · 2026Article
- Widespread genetic effect heterogeneity impacts bias and power in nonlinear Mendelian randomization.medRxiv : the preprint server for health sciences · 2026Article
- Iron status modulates immune cell proportions to drive epigenetic age acceleration: A 2-step Mendelian randomization study.Medicine · 2026Article
- Estimating the causal effect of cardiometabolic conditions on socioeconomic and healthcare outcomes: a scoping review of Mendelian randomization studies.Health economics review · 2026Article
- Thyroid function and risk of sepsis: a population-based prospective cohort study with traditional and genetic epidemiological analyses.Frontiers in endocrinology · 2026Article
- Associations of Genetically Predicted CKD With Urinary Tract Cancer and Lung Cancer: A Mendelian Randomization Analysis.Kidney medicine · 2025Article
- A flexible machine learning Mendelian randomization estimator applied to predict the safety and efficacy of sclerostin inhibition.American journal of human genetics · 2025Article
- Biological Age Acceleration, Genetic Susceptibility, and Incident Glaucoma Risk.Investigative ophthalmology & visual science · 2025Article
- Investigating whether smoking and alcohol behaviours influence risk of type 2 diabetes using a Mendelian randomisation study.Scientific reports · 2025Article
- Identification of effect modifiers using a stratified Mendelian randomization algorithmic framework.European journal of epidemiology · 2025Article
- Detecting Non-linear Dependence through Genome Wide Analysis.bioRxiv : the preprint server for biology · 2025Article
- Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study.Biomolecules · 2024Article
- Association between 25(OH) vitamin D and multiple sclerosis: cohort, shared genetics, and Causality.Nutrition journal · 2024Observational
- Positive and negative affect, related mental health traits, and cognitive performance: shared genetic architecture and potential causality.medRxiv : the preprint server for health sciences · 2024Article
- Article
- Causal inference in health and disease: a review of the principles and applications of Mendelian randomization.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- Association between alcohol consumption and incidence of dementia in current drinkers: linear and non-linear mendelian randomization analysis.EClinicalMedicine · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Mendelian randomization (MR) is a widely used method that exploits the unique properties of germline genetic variation to strengthen causal inference in relationships between exposures and outcomes. Nonlinear MR allows estimation of the shape of these relationships. In a previous paper, the authors applied linear and nonlinear MR to estimate the effect of BMI on mortality in UK Biobank, providing evidence for a J-shaped association. However, it is now clear that there are problems with widely used nonlinear MR methods, which draws attention to the likely erroneous nature of the conclusions regarding the shapes of several explored relationships. Here, the authors explore the utility and likely biases of these nonlinear MR methods with the use of a negative control design. Although there remains good evidence for a causal effect of higher BMI increasing the risk of mortality, the pattern of this association across different levels of BMI requires further characterization.
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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.