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Comment & Response
November 6, 2019

Heterogeneity Between Genetic Variants as a Proxy for Pleiotropy in Mendelian Randomization

Author Affiliations
  • 1Department of Epidemiology and Biostatistics, School of Public Health, St Mary’s Hospital, Imperial College London, London, United Kingdom
JAMA Cardiol. Published online November 6, 2019. doi:https://doi.org/10.1001/jamacardio.2019.4281

To the Editor Nazarzadeh et al1 are to be commended on their carefully conducted mendelian randomization (MR) study exploring the association of genetically determined systolic blood pressure with risk of valvular heart disease. The findings are interpreted in context, paying particular attention to existing research in the field as well as clinical relevance. The authors also perform a range of sensitivity analyses to investigate the robustness of their findings and are appropriately cautious in their interpretation. They acknowledge the potential limitations of the MR approach and that “its findings do not necessarily provide proof of causality.”1

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