【摘要】Maternal genetic and phenotypic characteristics (e.g., metabolic and behavioral) affect both the intrauterine milieu and lifelong health trajectories of their fetuses. Yet at the same time, fetal genotype may affect processes that alter pre and postnatal maternal physiology, and the subsequent health of both fetus and mother. We refer to these latter effects as ‘fetal drive.’ If fetal genotype is driving physiologic, metabolic, and behavioral phenotypic changes in the mother, there is a possibility of differential effects with different fetal genomes inducing different long-term effects on both maternal and fetal health, mediated through intrauterine environment. This proposed mechanistic path remains largely unexamined and untested. In this study, we offer a statistical method to rigorously test this hypothesis and make causal inferences in humans by relying on the (conditional) randomization inherent in the process of meiosis. We further propose conditioning on parental mating types (a function of parental genotypes) in Mendelian randomization (MR) to eliminate the need for one set of assumptions, thereby plausibly reducing bias, when confounding variables are correlated with the instrumental variable (in this case, a genetic/variant/marker). Through extensive simulation, we show that conditioning on parental mating types is a useful strategy to reduce the burden of assumptions and the potential bias in MR when the correlation between the instrument variable and confounders is due to assortative mating or population stratification but not linkage.