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

Publisher: Oxford University Press Country of Publication: England NLM ID: 7802871 Publication Model: Print Cited Medium: Internet ISSN: 1464-3685 (Electronic) Linking ISSN: 03005771 NLM ISO Abbreviation: Int J Epidemiol Subsets: MEDLINE

Original Publication: [London] Oxford University Press.

Mendelian Randomization Analysis*/methods ; Research Design*; Humans ; Bias

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.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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MC_UU_00032/1 United Kingdom MRC_ Medical Research Council; MR/M025209/1 United Kingdom MRC_ Medical Research Council; MC_UU_00011/1 United Kingdom MRC_ Medical Research Council; MM_UU_00011/3 United Kingdom MRC_ Medical Research Council; 29019 United Kingdom CRUK_ Cancer Research UK; MM_UU_00011/7 United Kingdom MRC_ Medical Research Council; NF-SI-0617-10145 United Kingdom DH_ Department of Health; C18281/A29019 United Kingdom CRUK_ Cancer Research UK

Keywords: Mendelian randomization; bias; genetic instrument; guideline; risk-of-bias assessment; tool

Date Created: 20220728 Date Completed: 20230210 Latest Revision: 20241001

20241001

PMC9908059

10.1093/ije/dyac149

35900265