ArticleInternational journal of epidemiology2022
Interpretation of Mendelian randomization using a single measure of an exposure that varies over time.
Article in International journal of epidemiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 5 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2024Pooled it
- Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.European journal of epidemiology · 2024Pooled it
- Major depressive disorder and the risk of irritable bowel syndrome: A Mendelian randomization study.Molecular genetics & genomic medicine · 2024Pooled it
- Pooled it
- Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis.BMC medicine · 2022Pooled it
- Psychiatric Risk in Chronic Spontaneous Urticaria: A Retrospective Cohort Study.Acta dermato-venereologica · 2026Article
- Multi-omics analysis of perfluorooctanoic acid and glioblastoma: insights from Mendelian randomization, network toxicology, and molecular docking.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- An evaluation of age-varying genetic effects underlying body-mass index and blood pressure in the UK Biobank.PLoS genetics · 2026Article
- Pre-diagnostic body mass index trajectories and associations with lung cancer risk.American journal of epidemiology · 2026Article
- Estimating the causal effect of cardiometabolic conditions on socioeconomic and healthcare outcomes: a scoping review of Mendelian randomization studies.Health economics review · 2026Article
- Integrated multi-omics identifies MCRS1 as a causal hub linking aging, metabolic syndrome, and breast cancer progression.International journal of surgery (London, England) · 2026Article
- A structural mean modeling Mendelian randomization approach to investigate the lifecourse effect of adiposity: applied and methodological considerations.American journal of epidemiology · 2026Article
- Mendelian Randomization Methods for Causal Inference: Estimands, Identification and Inference.Statistics in medicine · 2026Review
- Time-resolved Mendelian randomization detects substantial variation in the detrimental effect of obesity throughout life.Science advances · 2025Article
- ti-scMR: trajectory-inference-based dynamic single-cell Mendelian randomization identifies causal genes underlying phenotypic differences.NAR genomics and bioinformatics · 2025Article
- Evidence triangulation in health research.European journal of epidemiology · 2025Article
- Disentangling the effects of nicotine versus non-nicotine constituents of tobacco smoke on major depressive disorder: A multivariable Mendelian randomisation study.Addiction (Abingdon, England) · 2025Article
- The impact of sleep on breast cancer-specific mortality: a Mendelian randomisation study.BMC cancer · 2025Article
- Investigating causal effects of income on health using two-sample Mendelian randomisation.BMC global and public health · 2025Article
- Evaluating causal associations of chronotype with pregnancy and perinatal outcomes and its interactions with insomnia and sleep duration: a mendelian randomization study.BMC pregnancy and childbirth · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundMendelian randomization (MR) is a powerful tool through which the causal effects of modifiable exposures on outcomes can be estimated from observational data. Most exposures vary throughout the life course, but MR is commonly applied to one measurement of an exposure (e.g. weight measured once between ages 40 and 60 years). It has been argued that MR provides biased causal effect estimates when applied to one measure of an exposure that varies over time.
methodsWe propose an approach that emphasizes the liability that causes the entire exposure trajectory. We demonstrate this approach using simulations and an applied example.
resultsWe show that rather than estimating the direct or total causal effect of changing the exposure value at a given time, MR estimates the causal effect of changing the underlying liability for the exposure, scaled to the effect of the liability on the exposure at that time. As such, results from MR conducted at different time points are expected to differ (unless the effect of the liability on exposure is constant over time), as we illustrate by estimating the effect of body mass index measured at different ages on systolic blood pressure.
conclusionUnivariable MR results should not be interpreted as time-point-specific direct or total causal effects, but as the effect of changing the liability for the exposure. Estimates of how the effects of a genetic variant on an exposure vary over time, together with biological knowledge that provides evidence regarding likely effective exposure periods, are required to interpret time-point-specific causal effects.
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