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Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review
Francesca Spiga1,2, Mark Gibson2,3, Sarah Dawson1
1Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
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.
Insights
This study reviewed tools for assessing bias in Mendelian randomization (MR) studies. Seven tools evaluated address core assumptions, but require validation before widespread use in epidemiological research.
Area of Science:
- Epidemiology
- Genetic Epidemiology
- Biostatistics
Background:
- Mendelian randomization (MR) is increasingly used in epidemiology.
- This has led to a rise in systematic reviews of MR studies.
- Assessing bias and quality in MR studies is crucial for reliable evidence.
Purpose of the Study:
- To systematically review tools for assessing risk of bias and/or quality of evidence in MR studies.
- To review existing systematic reviews of MR studies.
Main Methods:
- Systematic literature search across multiple databases (MEDLINE, Embase, Web of Science, preprint servers, Google Scholar).
- Included articles containing tools for MR study assessment, reporting, and conducting.
- Collected data on tool characteristics, content, and bias assessment methods.
Main Results:
- Identified 14 tools, 35 systematic reviews, and 38 protocols.
- Seven tools specifically designed for MR bias/quality assessment were evaluated.
- All seven tools covered the three core assumptions of instrumental variable analysis.
Conclusions:
- An overview of bias assessment tools and methods for MR analysis is provided.
- Tools address instrumental variable assumptions, genetic instruments, population features, and traditional biases.
- Further validation of identified tools is needed before general recommendation for use.
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