Mendelian Randomization

Abstract

Causal claims from observational epidemiological studies are influenced by reverse causation and confounding. Mendelian randomization assesses whether genetic predictors of a risk factor (such as alcohol consumption) are associated with risk of a disease outcome (such as stroke). Due to Mendel's laws and the random nature of genetic inheritance, genetic variants are typically only associated with traits that they cause. This means genetic associations are less susceptible to confounding. Furthermore, as genetic variants are fixed from birth, the potential for reverse causation is diminished. Therefore, if the genetic variants affect the risk factor in a specific way (formally, if they satisfy the assumptions of an instrumental variable), then any genetic association with the outcome is indicative of a causal effect of the risk factor on the outcome. The approach has been used to strengthen (and refute) the causal nature of relationships for a wide range of risk factors and outcomes.