Evidence map›Paper›PMID 41567108›Full record

ArticleStatistics in medicine2026

Mendelian Randomization With Longitudinal Exposure Data: Simulation Study and Real Data Application.

Janne Pott, Marco Palma, Yi Liu, Jasmine A Mack, Ulla Sovio, Gordon C S Smith, Jessica Barrett, Stephen Burgess

Abstract read
In one paragraph

Article in Statistics in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Janne PottMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID https://orcid.org/0000-0002-5983-5331
Marco PalmaMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Yi LiuNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Jasmine A MackDepartment of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Ulla SovioDepartment of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Gordon C S SmithDepartment of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Jessica BarrettMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Stephen BurgessMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.

Funding

Medical Research Council MC_UU_00002/5Medical Research Council MC_UU_00002/7Medical Research Council MC_UU_00040/02Medical Research Council MR/V020595/1NIHR Cambridge Biomedical Research CentreWellcome Trust 225790Wellcome Trust 225790/Z/22/Z
6 · The paper itself

Abstract

BACKGROUND AND

aimMendelian randomization (MR) is a widely used tool to estimate causal effects using genetic variants as instrumental variables. MR is limited to cross-sectional summary statistics of different samples and time points to analyze time-varying effects. We aimed at using longitudinal summary statistics for an exposure in a multivariable MR setting and validating the effect estimates for the mean, slope, and within-individual variability. SIMULATION STUDY: We tested our approach in 12 scenarios for power and type I error, depending on shared instruments between the mean, slope, and variability, and regression model specifications. We observed high power to detect causal effects of the mean and slope throughout the simulation, but the variability effect was low powered in the case of shared SNPs between the mean and variability. Mis-specified regression models led to lower power and increased the type I error. REAL DATA APPLICATION: We applied our approach to two real data sets (POPS, UK Biobank). We detected significant causal estimates for both the mean and the slope in both cases, but no independent effect of the variability. However, we only had weak instruments in both data sets.

conclusionWe used a new approach to test a time-varying exposure for causal effects of the exposure's mean, slope and variability. The simulation with strong instruments seems promising but also highlights three crucial points: (1) The difficulty to define the correct exposure regression model, (2) the dependency on the genetic correlation, and (3) the lack of strong instruments in real data. Taken together, this demands a cautious evaluation of the results, accounting for known biology and the trajectory of the exposure.

Indexed as

Mendelian Randomization AnalysisComputer SimulationHumansLongitudinal StudiesModels, StatisticalPolymorphism, Single NucleotideRegression AnalysisUK Biobank

Identifiers

PMID41567108
PMCPMC12824831

What Socratic holds

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Registered trials

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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 Socratic graph.