Genetic evidence for independent causal relationships between metabolic biomarkers and risk of coronary artery diseases

Hooman Allayee

doi:10.1016/j.jlr.2021.100064

Abstract

Decades of epidemiological research have identified numerous risk factors and biomarkers that are associated with risk of coronary artery disease (CAD) and myocardial infarction. The most well recognized of these are circulating levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides, as well as metabolic syndrome-related traits, such as obesity, hypertension, and T2D (1). However, the association of a biomarker with CAD in observational studies does not necessarily prove a causal relationship.

Highlights

Decades of epidemiological research have identified numerous risk factors and biomarkers that are associated with risk of coronary artery disease (CAD) and myocardial infarction
CAD and dozens of CAD-associated biomarkers, there have been numerous opportunities for testing causality by Mendelian randomization (MR). Proof that this approach can be successful comes from observations that LDL-raising alleles are causally and dose dependently associated with increased risk of CAD (9), which are consistent with the magnitude of dose-dependent decreases in CAD risk observed in clinical trials as a function of the degree of LDL lowering (10)
MR analyses have not provided evidence for a causal role of HDL in CAD (12) and generated debate as to the relevance of HDL in the pathogenesis of atherosclerosis and as a therapeutic target (13). In this issue of the Journal of Lipid Research, Thomas et al (14) carried out a series of MR analyses to test the causal relationship between traditional CAD risk factors, including LDL, HDL triglycerides, BMI, T2D, systolic blood pressure, and risk of CAD (In Press)

Summary

Introduction

Decades of epidemiological research have identified numerous risk factors and biomarkers that are associated with risk of coronary artery disease (CAD) and myocardial infarction. In this issue of the Journal of Lipid Research, Thomas et al (14) carried out a series of MR analyses to test the causal relationship between traditional CAD risk factors, including LDL, HDL triglycerides, BMI, T2D, systolic blood pressure, and risk of CAD (In Press).

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