Evidence mapPaperPMID 41999635Full record

SynthesisInternational journal of epidemiology2026

Structured tools for assessing quality and risk of bias in Mendelian randomization studies: an updated systematic review.

Jinyue Yu, Mengxuan Zou, Francesca Spiga, Sarah Dawson, George Davey Smith, Julian P T Higgins

Abstract readSystematic Review
In one paragraph

Synthesis in International journal of epidemiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Jinyue YuPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0001-5182-3232
Mengxuan ZouPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Francesca SpigaPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-6904-2247
Sarah DawsonPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
George Davey SmithPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-1407-8314
Julian P T HigginsPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-8323-2514

Funding

Cancer Research UK C18281/A29019Integrative Cancer Epidemiology Programme (ICEP)Medical Research Council MC_UU_00032/1MRC Integrative Epidemiology Unit at the University of BristolNational Institute for Health and Care Research (NIHR) NIHR203807NIHR Applied Research Collaboration West (ARC West) at University Hospitals BristolNIHR Bristol Evidence Synthesis Group NIHR153861NIHR Bristol-UCL-King's Living Evidence Synthesis Group NIHR168894Weston NHS Foundation Trust NIHR200181
6 · The paper itself

Abstract

backgroundThe growing use of Mendelian randomization (MR) has heightened the need for rigorous quality and bias assessment tools. A previous systematic review included studies published up to July 2021 identified 14 structured instruments for conducting, evaluating, and reporting MR studies. However, methodological developments have accelerated in the years since.

methodsWe updated the previous systematic review to include tools published between July 2021 and January 2025, applying the same search strategy and eligibility criteria. Two reviewers independently screened articles, extracted data, and mapped tool content to bias domains.

resultsWe identified 15 additional articles, bringing the total to 29 tools. Of these 29, 19 provided structured evaluation tools. Twelve of the 19 evaluation tools were newly added in the present review, which addressed broader methodological domains beyond core instrumental variable assumptions, including genetic instrument selection, population stratification, sensitivity analyses, and dataset considerations. However, substantial variation in bias domains, structure, and scoring methods across tools persists. Key gaps remain in the assessment of linkage disequilibrium, missing data, and dynastic effects.

conclusionsWhile the number of structured tools has increased in recent years, the lack of standardization across tools makes it difficult to compare across systematic reviews of MR studies. Developing more complete and standardized evaluation frameworks and properly testing these tools in practice are important next steps to improve the overall quality of MR research.

Indexed as

Mendelian Randomization AnalysisResearch DesignBiasHumansevaluation toolsMendelian randomizationquality assessmentrisk of biassystematic review

Identifiers

PMID41999635
PMCPMC13091611

What Socratic holds

Textmetadata
LicenceCC BY
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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.