Insights into Causal Cardiovascular Risk Factors from Mendelian Randomization

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.

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. 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.