Insights into Causal Cardiovascular Risk Factors from Mendelian Randomization

Abstract

Purpose of the Review: This review summarizes major insights into causal risk factors for cardiovascular disease (CVD) by using Mendelian randomization (MR) to obtain unconfounded estimates, contextualized within its strengths and weaknesses. Recent Findings: MR studies have confirmed the role of major CVD risk factors, including alcohol, smoking, adiposity, blood pressure, type 2 diabetes, lipids, and possibly inflammation, but added that the relation with alcohol is likely linear, confirmed the role of diastolic blood pressure, identified apolipoprotein B as the major target lipid, and foreshadowed results of some trials concerning anti-inflammatories. Identifying a healthy diet and the role of early life influences, such as birth weight, has proved more difficult. Summary: Use of MR has winnowed empirically driven hypotheses about CVD into a set of genetically validated targets of intervention. Greater inclusion of global diversity in genetic studies and the use of an overarching framework would enable even more informative MR studies.