Tools for assessing quality and risk of bias in Mendelian randomization studies: A systematic review

Francesca Spiga; Mark Gibson; Sarah Dawson; Kate Tilling; George Davey Smith; Marcus R. Munafo; Julian P.T. Higgins

doi:10.1093/ije/dyac149

Tools for assessing quality and risk of bias in Mendelian randomization studies: A systematic review

Francesca Spiga
, Mark Gibson
, Sarah Dawson
, Kate Tilling
, George Davey Smith
, Marcus R. Munafo
, Julian P.T. Higgins

Vice Chancellor's Office

University of Bristol
MRC Integrative Epidemiology Unit

Research output: Contribution to journal › Article › peer-review

74 Citations (SciVal)

Abstract

Background: The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for assessing risk of bias and/or quality of evidence in MR studies and a review of systematic reviews of MR studies.

Methods: We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR studies. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment.

Results: Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates.

Conclusion: We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. Issues commonly addressed relate to the three standard assumptions of instrumental variables analyses, the choice of genetic instrument(s) and features of the population(s) from which the data are collected (particularly in two-sample MR), in addition to more traditional non-MR-specific epidemiological biases. The identified tools should be tested and validated for general use before recommendations can be made on their widespread use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.

Original language	English
Pages (from-to)	227-249
Number of pages	23
Journal	International Journal of Epidemiology
Volume	52
Issue number	1
Early online date	1 Feb 2023
DOIs	https://doi.org/10.1093/ije/dyac149
Publication status	Published - 1 Feb 2023

Data Availability Statement

All materials used in this study are available in the Supplementary material, available as Supplementary data at IJE online, or the main text.

Funding

This work was supported by a Cancer Research UK programme grant (the Integrative Cancer Epidemiology Programme C18281/A29019 to F.S. and M.R.M.). G.D.S., K.T. and M.R.M. are part of the Medical Research Council Integrative Epidemiology Unit (MRC IEU) at the University of Bristol (MC_UU_00011/1 to G.D.S.; MM_UU_00011/3 to K.T.; MM_UU_00011/7 to M.R.M.). J.P.T.H. is a National Institute for Health Research (NIHR) Senior Investigator (NF-SI-0617–10145) and is supported by NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by the NIHR Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust.

Keywords

bias
genetic instrument
guideline
Mendelian randomization
risk-of-bias assessment
tool

ASJC Scopus subject areas

Epidemiology

Access to Document

10.1093/ije/dyac149Licence: CC BY

Cite this

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title = "Tools for assessing quality and risk of bias in Mendelian randomization studies: A systematic review",

abstract = "Background: The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for assessing risk of bias and/or quality of evidence in MR studies and a review of systematic reviews of MR studies. Methods: We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR studies. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment. Results: Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates. Conclusion: We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. Issues commonly addressed relate to the three standard assumptions of instrumental variables analyses, the choice of genetic instrument(s) and features of the population(s) from which the data are collected (particularly in two-sample MR), in addition to more traditional non-MR-specific epidemiological biases. The identified tools should be tested and validated for general use before recommendations can be made on their widespread use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.",

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author = "Francesca Spiga and Mark Gibson and Sarah Dawson and Kate Tilling and \{Davey Smith\}, George and Munafo, \{Marcus R.\} and Higgins, \{Julian P.T.\}",

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AU - Dawson, Sarah

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AU - Munafo, Marcus R.

AU - Higgins, Julian P.T.

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AB - Background: The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for assessing risk of bias and/or quality of evidence in MR studies and a review of systematic reviews of MR studies. Methods: We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR studies. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment. Results: Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates. Conclusion: We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. Issues commonly addressed relate to the three standard assumptions of instrumental variables analyses, the choice of genetic instrument(s) and features of the population(s) from which the data are collected (particularly in two-sample MR), in addition to more traditional non-MR-specific epidemiological biases. The identified tools should be tested and validated for general use before recommendations can be made on their widespread use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.

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Tools for assessing quality and risk of bias in Mendelian randomization studies: A systematic review

Abstract

Data Availability Statement

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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