Edward H. Livingston
uses genetic variants to determine whether an observational association between a risk factor and an outcome is consistent with a potential causal effect.90
91 Mendelian randomization relies on the natural, random assortment of genetic variants during meiosis, yielding a random distribution of genetic variants in a population. Individuals are naturally assigned at birth to inherit a genetic variant that affects a risk factor (eg, a gene variant that raises low-density lipoprotein cholesterol [LDL-C] levels) or not to inherit such a variant. Individuals who carry the variant and those who do not are then followed up for the development of an outcome of interest. Because these genetic variants may be unassociated with confounders, differences in the outcome between those who carry the variant and those who do not can be attributed to the difference in the risk factor. For example, a genetic variant associated with higher LDL-C levels that also is associated with a higher risk of coronary heart disease may provide supportive evidence to infer a potential causal effect of LDL-C on coronary heart disease....