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The Pros and Cons of Mendelian Randomization Studies to Evaluate Emerging Cardiovascular Risk Factors

  • Novel and Emerging Risk Factors (Khurram Nasir, Section Editor)
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Abstract

Purpose of Review

Mendelian randomization (MR) is a technique that uses natural genetic variation to assess the potential causal role of a modifiable risk factor on cardiovascular disease. Advances have led to the identification of single nucleotide polymorphisms linked with risk factors that act as naturally randomized instruments to investigate the risk factor-disease relationship.

Recent Findings

There are several pros and cons when using MR. It can address many limitations of observational study design including confounding, reverse causation, and demonstration of causality when a randomized controlled trial is not practical or feasible. However, several limitations do exist and include pleiotropy (multiple downstream effects of a single genetic variant), linkage disequilibrium (non-random association of genetic variation), and imprecise estimates of causal effects.

Summary

MR is an important tool in cardiovascular research and has been applied to assess cardiovascular risk factors including obesity and atrial fibrillation. While these studies provide insight into disease causation, understanding the strengths and limitations of the technique is important for appropriate interpretation of results.

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Funding

Dr. Neeland is supported by grant K23DK106520 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health and by the Dedman Family Scholarship in Clinical Care from UT Southwestern.

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  1. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-8830, USA

    Jainy Savla & Ian J. Neeland

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Dr. Neeland reports personal fees from Boehringer-Ingelheim, American Heart Association, and from Advanced MR Analytics AB, plus grants from Novo Nordisk.

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This article is part of the Topical Collection on Novel and Emerging Risk Factors

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Savla, J., Neeland, I.J. The Pros and Cons of Mendelian Randomization Studies to Evaluate Emerging Cardiovascular Risk Factors. Curr Cardiovasc Risk Rep 12, 2 (2018). https://doi.org/10.1007/s12170-018-0566-9

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