Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps

Current Opinion in Lipidology
Brian A Ference

Abstract

Mendelian randomization studies have the potential to transform our understanding of cardiovascular medicine by generating naturally randomized data that can fill evidence gaps when a randomized trial would be either impossible or impractical to conduct. Here, we review recent Mendelian randomization studies evaluating the effect of low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD). Mendelian randomization studies consistently demonstrate that LDL-C is causally associated with the risk of CHD. Furthermore, exposure to genetically mediated lower LDL-C appears to be associated with a much greater than expected reduction in CHD risk, thus suggesting that LDL-C has a cumulative effect on the risk of CHD. In addition, genetically mediated lower LDL-C is log-linearly associated with the risk of CHD and the effect of polymorphisms in multiple different genes on the risk of CHD is remarkably consistent when measured per unit lower LDL-C. The naturally randomized genetic evidence suggests that LDL-C has a causal and cumulative effect on the risk of CHD, and that the clinical benefit of exposure to lower LDL-C is determined by the absolute magnitude of exposure to lower LDL-C independent of the mecha...Continue Reading

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Citations

Mar 13, 2017·Revista Española De Cardiología·Fernando Civeira, Nuria Plana
Mar 20, 2018·Current Opinion in Lipidology·Laurent Yvan-Charvet, Bertrand Cariou
Oct 18, 2018·Current Cardiology Reports·Lane B BenesMichael H Davidson
Aug 20, 2019·Nature Reviews. Disease Primers·Peter LibbyEldrin F Lewis
Jul 14, 2017·Journal of Lipid Research·Andrew C MartinGerald F Watts
Jun 23, 2019·Current Cardiology Reports·Julius L Katzmann, Ulrich Laufs
Jan 14, 2017·Der Internist·A Vogt
Mar 17, 2019·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Andrea Poli, Francesco Visioli
Mar 5, 2020·Journal of Community Hospital Internal Medicine Perspectives·Yousuf ZafarLaura Schmidt
Nov 24, 2020·Journal of the American Heart Association·Peter WilleitSotirios Tsimikas
Dec 10, 2020·Nutrients·Kalliopi Karatzi On Behalf Of The Feel Diabetes-Study Group
May 11, 2021·Clínica e investigación en arteriosclerosis : publicación oficial de la Sociedad Española de Arteriosclerosis·Carlos Guijarro, Juan Cosín-Sales

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