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Research Methods & Reporting

Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k601 (Published 12 July 2018) Cite this as: BMJ 2018;362:k601
  1. Neil M Davies, research fellow12,
  2. Michael V Holmes, university research lecturer1345,
  3. George Davey Smith, professor126
  1. 1Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, UK
  2. 2Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 2BN, UK
  3. 3Medical Research Council Population Health Research Unit, University of Oxford, UK
  4. 4Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.
  5. 5National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK
  6. 6National Institute for Health Research Bristol Biomedical Research Centre, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
  1. Correspondence: G Davey Smith pa-ieudirector{at}bristol.ac.uk
  • Accepted 4 December 2017

Mendelian randomisation uses genetic variation as a natural experiment to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data. As with all epidemiological approaches, findings from Mendelian randomisation studies depend on specific assumptions. We provide explanations of the information typically reported in Mendelian randomisation studies that can be used to assess the plausibility of these assumptions and guidance on how to interpret findings from Mendelian randomisation studies in the context of other sources of evidence

Summary points

  • Mendelian randomisation is a research method that provides evidence about putative causal relations between modifiable risk factors and disease, using genetic variants as natural experiments

  • Mendelian randomisation is less likely to be affected by confounding or reverse causation than conventional observational studies

  • Like all analytical approaches, however, Mendelian randomisation depends on assumptions, and the plausibility of these assumptions must be assessed

  • Moreover, the relevance of the results for clinical decisions should be interpreted in light of other sources of evidence

  • We provide a critical appraisal checklist that can be used to assess and interpret Mendelian randomisation studies

Understanding whether a biomarker or behaviour causes ill health is central to evidence based medicine, drug development, and better informed clinical decision making. Ideally, evidence of causal effects comes from well conducted randomised trials. Clinicians are well versed in the strengths and limitations of such trials and have an increasingly sophisticated understanding of traditional analyses of observational studies. But they may be less aware of the strengths and limitations of a more recently developed approach to analysing observational data known as Mendelian randomisation. Although numerous guides exist for conducting123 and reporting Mendelian randomisation studies and related methods,45 here we focus on helping clinicians and practitioners read and interpret them. Our goal is to provide explanations of core …

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