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October 14, 2019

Mendelian Randomization—A Journey From Obscurity to Center Stage With a Few Potholes Along the Way

Author Affiliations
  • 1Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland
  • 2Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
  • 3Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
  • 4Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, United Kingdom
  • 5Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland
  • 6Department of Neurology, Johns Hopkins University, Baltimore, Maryland
JAMA Neurol. 2020;77(1):7-8. doi:10.1001/jamaneurol.2019.3419

In 1986, Katan1 described a novel method to reliably estimate the effects of a causal variable without the need to conduct a traditional controlled trial.2 Now known as mendelian randomization (MR), this approach relies on the random assortment of genes (and noncoding DNA) as described by Mendel’s second law of inheritance. At the kernel of MR is the notion that this shuffling of DNA evenly distributes confounding factors, and this pattern, which remains unaltered through the lifetime of an individual, can be used to simulate the effect of modifiable factors (exposures) on susceptibility to a disease (outcome).3

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