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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

83 Citations (Scopus)

190 Downloads (Pure)

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
Article number	dyac149
Number of pages	23
Journal	International Journal of Epidemiology
DOIs	https://doi.org/10.1093/ije/dyac149
Publication status	Published - 28 Jul 2022

Research Groups and Themes

ICEP
TARG

Keywords

Mendelian randomization
genetic instrument
bias
tool
guideline
risk of bias assessment

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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research
IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Cite this

@article{b0fcdaa529c042c08c9b2e62808f1546,

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.",

keywords = "Mendelian randomization, genetic instrument, bias, tool, guideline, risk of bias assessment",

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

year = "2022",

month = jul,

day = "28",

doi = "10.1093/ije/dyac149",

language = "English",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

}

TY - JOUR

T1 - Tools for assessing quality and risk of bias in Mendelian randomization studies

T2 - a systematic review

AU - Spiga, Francesca

AU - Gibson, Mark

AU - Dawson, Sarah

AU - Tilling, Kate M

AU - Davey Smith, George

AU - Munafo, Marcus R

AU - Higgins, Julian P T

PY - 2022/7/28

Y1 - 2022/7/28

N2 - 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.

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.

KW - Mendelian randomization

KW - genetic instrument

KW - bias

KW - tool

KW - guideline

KW - risk of bias assessment

U2 - 10.1093/ije/dyac149

DO - 10.1093/ije/dyac149

M3 - Article (Academic Journal)

C2 - 35900265

SN - 0300-5771

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

M1 - dyac149

ER -

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

Abstract

Research Groups and Themes

Keywords

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

Cite this