Mendelian randomisation studies: principle and selected examples from cardiovascular medicine

Authors: Jaroslav A. Hubáček 1,2
Authors‘ workplace: Centrum experimentální medicíny, IKEM, Praha 1;  III. interní klinika – klinika endokrinologie a metabolismu 1. LF UK a VFN v Praze 2
Published in: AtheroRev 2020; 5(3): 176-180


Mendelian randomizations (MR) are studies that have been experiencing an unprecedented boom in last decade, although the principle is known for almost half of century. The sequencing of human genome and GWAs studies help us to understood the genetic mosaic of human diseases and has identified a hundreds of variants associated with cardiovascular disease. The fundament of mendelian randomization is to use a genetic marker to investigate, if there is a causal relationship between a biomarker and risk of disease. The principle is that, if genetic marker is associated with level of the biomarker, it needs to be in similar extent associated also with the disease risk and the causal relationship is confirmed. If the biomarker is genotype-associated but not disease-related, then the causality “parameter → disease” does not apply. For example, causality between plasma triglycerides and CVD risk or between statin therapy and an increased risk of T2DM has been proved by MR. In contrast, HDL-cholesterol levels or CRP levels have not been proven causal for CVD development. The myth of the protective effect of alcohol consumption on CVD risk was disproved. These findings may have a major impact on treatment – pharmacotherapy of non-causal factors will fails and can be even dangerous for the patients.


genetic – prediction – CVD – genome wide association studies (GWAS) – mendelian randomization

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