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Publications

Journal Article Review Epublish 3 citations

PubMed: 40547872 DOI: 10.5334/gh.1438

Mendelian Randomisation: Concepts, Opportunities, Challenges, and Future Directions.

Glob Heart 20(1):54

Authors: Sophie C de Ruiter, Lena Tschiderer, Diederick E Grobbee, Peter Willeit, Hester M den Ruijter, A Floriaan Schmidt, Sanne A E Peters

Affiliations

  • Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria.
  • Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria.
  • Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
  • Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands.
  • Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, United Kingdom.
  • Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • UCL British Heart Foundation Research Accelerator, London, United Kingdom.
  • The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom.

Abstract

Mendelian randomisation is an approach in genetic epidemiology that uses genetic variants as instrumental variables to investigate the causal relationship between genetically proxied exposures and health outcomes. During the last years, the number of published Mendelian randomisation studies increased tremendously. There are several opportunities of Mendelian randomisation including obtaining potential causal relationships between both exogenous and endogenous exposures and outcomes and for identifying and prioritising drug-targets to inform clinical trials. However, it is also important to be aware of its challenges. This includes the reliability of results under the assumptions on instrumental variables, being aware of potential biases, the correct and critical interpretation of findings and comparison to the results of randomised controlled trials, as well as the availability of genetic data on specific subgroups. This review provides a comprehensive overview of the opportunities and challenges of Mendelian randomisation and presents key future perspectives.