Because genotypes are assigned randomly when passed from parents to offspring during meiosis, if we assume that mate choice is not associated with genotype (panmixia), then the population genotype distribution should be unrelated to the confounding factors that typically plague observational epidemiology studies. In this regard, Mendelian randomization can be thought of as a “naturally” randomized controlled trial. Because the polymorphism is the instrument, Mendelian randomization is dependent on prior genetic association studies having provided good candidate genes for response to risk exposure.