Parent-offspring transmission of drug abuse and alcohol use disorder: Application of the multiple parenting relationships design.

With complete genealogical and cohabitation information, new genetic-epidemiological designs can be developed to clarify causes of parent-offspring transmission. We propose the Multiple Parenting Relationships (MPR) Design and apply it to drug abuse (DA) and alcohol use disorder (AUD). Using national Swedish registries, we identified four kinds of informative parents with multiple children with whom they had different genetic and/or rearing relationships. These types had children for whom they provided: (a) genes (G) plus rearing (R), G only and R only; (b) G + R and G only; (c) G only and R only; and (d) G + R and R only. We identified DA and AUD cases from national registries in over 475,000 informative parent-offspring pairs. Controlling for parental resemblance for DA or AUD, all estimates were statistically homogeneous across family types. The weighted average tetrachoric correlation (SE) for DA for G + R, R only and G only relationships were, respectively, +0.21 (0.01), +0.10 (0.02), and +0.16 (0.02). Parallel results for AUD were +0.16 (0.01), +0.04 (0.02), and +0.14 (0.01). Analyses within families with affected parents showed significantly higher disorder risks in offspring with a G + R versus an R only relationship. The MPR design is complementary to other methods, especially adoption and triparental designs, in clarifying the sources of cross-generational transmission. Consistent with results from these other designs applied to the Swedish population, we find that for DA and AUD, parent-offspring resemblance was strongest for G + R relationships, intermediate for G only relationships and weakest but significant for R only relationships.