We used an extended nature of nurture design45, 46, depicted in Figure 1, to examine the mechanisms through which parental genotypes influence offspring outcomes. In this model, paternal (P) and maternal (M) genotypes are partitioned into those that are shared with offspring (i.e., transmitted alleles, T) and those that are not shared with offspring (i.e., nontransmitted alleles, NT). This cross-generational allele sharing information can be used to construct separate genome-wide polygenic scores that represent the portion of each parent’s ‘genetic loading’ for a trait or disorder, such as AUDSx, that is directly transmitted to the offspring, and that which is indirectly transmitted to the offspring via the environment through a ‘genetic nurture’ pathway. We expanded this design to examine whether the parental divorce and relationship discord composite measures mediate both the effects of transmitted and nontransmitted alleles. In addition, we included matching parental alcohol use phenotypes as mediators of the intergenerational transmission of genetic risk.
