Mendelian randomization for cardiovascular diseases: principles and applications

• Published in: European heart journal Vol. 44; no. 47; pp. 4913 - 4924
• Main Authors: Larsson, Susanna C, Butterworth, Adam S, Burgess, Stephen
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 14.12.2023
• Subjects: Cardiovascular disease; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Causality; Genetics; Genome-Wide Association Study; Humans; Mendelian randomization; Mendelian Randomization Analysis - methods; Risk Factors; Single nucleotide polymorphisms; State of the Art Review; Cardiovascular disease; Genetics; Mendelian randomization; Single nucleotide polymorphisms
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehad736

Abstract Large-scale genome-wide association studies conducted over the last decade have uncovered numerous genetic variants associated with cardiometabolic traits and risk factors. These discoveries have enabled the Mendelian randomization (MR) design, which uses genetic variation as a natural experiment to improve causal inferences from observational data. By analogy with the random assignment of treatment in randomized controlled trials, the random segregation of genetic alleles when DNA is transmitted from parents to offspring at gamete formation is expected to reduce confounding in genetic associations. Mendelian randomization analyses make a set of assumptions that must hold for valid results. Provided that the assumptions are well justified for the genetic variants that are employed as instrumental variables, MR studies can inform on whether a putative risk factor likely has a causal effect on the disease or not. Mendelian randomization has been increasingly applied over recent years to predict the efficacy and safety of existing and novel drugs targeting cardiovascular risk factors and to explore the repurposing potential of available drugs. This review article describes the principles of the MR design and some applications in cardiovascular epidemiology. Graphical Abstract Graphical Abstract Mendelian randomization findings on major cardiometabolic and lifestyle factors and common cardiovascular diseases.