Cited by 3,994Meta-analysis and systematic reviewsGenetic Associations and EpidemiologyStatistical Methods in Epidemiology

The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index; none of the 10 sources its claims cite is checked for support yet.

Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement

Open access

Abstract

Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation. Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validity of MR-specific assumptions should be well reported. An item on data sharing includes reporting when the data and statistical code required to replicate the analyses can be accessed. Conclusions and Relevance: STROBE-MR provides guidelines for reporting MR studies. Improved reporting of these studies could facilitate their evaluation by editors, peer reviewers, researchers, clinicians, and other readers, and enhance the interpretation of their results.

Overview

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Written from the paper’s full text.

TL;DR

The STROBE-MR Statement is a reporting guideline for Mendelian randomization (MR) studies, developed as a stand-alone extension of STROBE using EQUATOR guidance. It provides a 20-item, 30-subitem checklist covering 1-sample and 2-sample MR studies and emphasizes transparent reporting of MR-specific assumptions, validity assessments, and data/code availability.

Key findings

  • The final STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems.
  • It covers both 1-sample and 2-sample MR studies assessing one or multiple exposures and outcomes, including MR studies that follow a genome-wide association study and are reported in the same article.
  • Pilot testing on 20 MR articles published in 2018 found reporting deficiencies: none of the 10 2-sample MR studies described the underlying exposure and outcome study populations in detail, compared them, or discussed sample overlap; only 10 studies (50%) reported efforts to test and correct for possible pleiotropy; details on imputation of missing genetic data or minor allele frequency cutoffs were missing in 11 of 20 articles (55%); instrument strength was reported in 10 (50%); 10 (50%) lacked discussion of clinical or public health relevance; and 13 (65%) did not address generalizability.
  • The checklist asks authors to justify why MR is helpful, state prespecified causal hypotheses, describe measurement/quality/selection of genetic variants, report assessment of MR assumptions, and report where data and statistical code can be accessed.

Methods

  • Development followed the EQUATOR framework, used STROBE as a starting point, and was initiated in 2018 by reviewing literature on reporting of instrumental variable and MR studies.
  • A group of 17 experts participated in a May 2019 workshop; the draft checklist was published as a preprint in July 2019, revised through 2020, and finalized in July 2021.
  • The draft checklist was pilot-tested on a random sample of 20 original MR articles published in 2018 (10 one-sample and 10 two-sample), selected from 404 potentially eligible articles as of April 1, 2019; this was not intended as a systematic review.

Limitations

  • The paper states that the statement does not describe all methods that can be used to assess all assumptions required in an MR study, although major assumptions and commonly used methods are described.
  • The paper states that, as a consensus document, it will be updated with further community feedback, and that no systematic review was undertaken to better understand reporting deficiencies in MR studies.
  • Evident from the text: no formal Delphi process was performed, the pilot review was not a systematic review, and the checklist is explicitly not intended as an instrument to evaluate MR research quality.

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Integrity signals

Registry

Crossref · 10.1001/jama.2021.18236

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

13 Not checked yet · 11 Own method · 11 No basis given · 8 Own result · 1 Own interpretation

Verify all 10 references — free account

Show all 8 claims

  • Probably not a substantial claim. 33
  • It may state two separate claims as one. 17
36 of 36
  • The paper relies on this without support.

    Mendelian randomization studies use genetic variants that are reliably associated with exposures of interest but do not vary with correlated lifestyle or socioeconomic factors that may confound conventional observational associations.

    “Mendelian randomization studies use genetic variants, typically single-nucleotide polymorphisms (SNPs), that are reliably associated with exposures of interest but do not vary with the correlated lifestyle or socioeconomic factors that may confound conventional observational associations.”
  • The paper relies on this without support.

    The number of published Mendelian randomization studies increased from 1 report in 2003 to more than 800 articles in 2020.

    “In recent decades, the number of published mendelian randomization studies has increased rapidly, from 1 report in 2003 to more than 800 articles in 2020.”
  • The paper relies on this without support.

    The 20 randomly selected 2018 Mendelian randomization articles are representative enough to confirm reporting deficiencies in Mendelian randomization studies.

    “Of 404 potentially eligible articles (as of April 1, 2019), 20 were randomly selected and scanned to determine whether they contained original research.”
  • The paper relies on this without support.

    The expert consensus process used, without a formal Delphi process, yields a valid reporting guideline.

    “A formal Delphi process was not performed.”
  • The paper relies on this without support.

    Reporting of mendelian randomization studies is currently deficient and stands to be improved.

    “Third, a systematic review has not been undertaken to better understand reporting deficiencies in mendelian randomization studies.”
5 of 5

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Citations

Cites

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Research works printed but not linked: 1

  1. MRC Integrative Epidemiology Unit, University of Bristol. 4th Mendelian Randomization Conference 2019. Accessed July 10, 2019. https://www.bristol.ac.uk/integrative-epidemiology/seminars/2019/mr-conference-2019.html

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Metadata

Authors
Skrivankova, V. W., Richmond, R. C., Woolf, B. A. R., Yarmolinsky, J., Davies, N. M., Swanson, S. A., VanderWeele, T. J., Higgins, J. P. T., Timpson, N. J., Dimou, N., Langenberg, C., Golub, R. M., Loder, E. W., Gallo, V., Tybjaerg-Hansen, A., Davey Smith, G., Egger, M., & Richards, J. B.
Affiliations
  • University of Bern (CH)
  • University of Bristol (GB)
  • Norwegian University of Science and Technology (NO)
  • Erasmus MC (NL)
  • Harvard University (US)
  • Centre international de recherche sur le cancer (FR)
  • University of Cambridge (GB)
  • Northwestern University (US)
  • Brigham and Women's Hospital (US)
  • University of London (GB)
  • Section for Molecular Genetics, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
Corresponding author
Richards, J. Brent
Venue
JAMA
Published
2021-10-26
Volume
326
Issue
16
Pages
1614
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
OpenAlex
W3210570897
Cited by
3,994
References
31
Citations by year
2026: 711 · 2025: 1296 · 2024: 1358 · 2023: 470 · 2022: 153 · 2021: 4
FWCI
297.95
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • JAMA (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
  • BORIS (University Library Bern) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
  • Explore Bristol Research (submittedVersion)
Funders
  • World Health Organization
  • Wellcome Trust (202802/Z/16/Z)
  • National Institute for Health and Care Research (NF-SI-0617-10145)
  • Medical Research Council (MC_UU_00011/5, MC_UU_00011/1)
  • Economic and Social Research Council (2094259)
Topics
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords
Mendelian randomization, reporting guidelines, reporting checklist, observational studies, causal inference, instrumental variables, genetic variants, confounding, reverse causality, data sharing, reproducibility, EQUATOR Network
MeSH terms
Epidemiology, Humans, Pilot Projects, Bias, Guidelines as Topic, Information Dissemination, Genome-Wide Association Study, Mendelian Randomization Analysis, Checklist, Social Media, Observational Studies as Topic

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