Factorial Mendelian randomization: using genetic variants to assess interactions.

International Journal of Epidemiology
Jessica MB ReesStephen Burgess

Abstract

Factorial Mendelian randomization is the use of genetic variants to answer questions about interactions. Although the approach has been used in applied investigations, little methodological advice is available on how to design or perform a factorial Mendelian randomization analysis. Previous analyses have employed a 2 × 2 approach, using dichotomized genetic scores to divide the population into four subgroups as in a factorial randomized trial. We describe two distinct contexts for factorial Mendelian randomization: investigating interactions between risk factors, and investigating interactions between pharmacological interventions on risk factors. We propose two-stage least squares methods using all available genetic variants and their interactions as instrumental variables, and using continuous genetic scores as instrumental variables rather than dichotomized scores. We illustrate our methods using data from UK Biobank to investigate the interaction between body mass index and alcohol consumption on systolic blood pressure. Simulated and real data show that efficiency is maximized using the full set of interactions between genetic variants as instruments. In the applied example, between 4- and 10-fold improvement in efficienc...Continue Reading

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Citations

May 8, 2020·International Journal of Epidemiology·Dylan M Williams
Aug 12, 2020·Genetic Epidemiology·Zhi Ming Xu, Stephen Burgess
Dec 5, 2019·International Journal of Epidemiology·Jeremy A Labrecque, Sonja A Swanson
Jun 13, 2020·Journal of Neurology·Marijne Vandebergh, An Goris
Nov 17, 2020·Frontiers in Genetics·Chen ZhuQiran Zhao
Mar 23, 2021·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Laurie J Hannigan, Alexandra Havdahl
May 8, 2021·European Journal of Epidemiology·Alice R CarterLaura D Howe
Jun 6, 2021·Molecular Psychiatry·Robyn E WoottonHannah M Sallis
Aug 13, 2021·PLoS Computational Biology·Sarah A Gagliano Taliun, David M Evans

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