Cross-generational transmission of genetic risk for alcohol and drug use disorders: the impact of substance availability on the specificity of genetic risk.

Background: Among individuals with alcohol use disorder (AUD) and drug use disorder (DUD), is their genetic liability and its specificity moderated by substance availability?

Methods: Offspring (born 1960-1995) and their biological parents from three family types [not-lived-with (NLW) biological father, mother and adoptive] and their AUD and DUD diagnoses were ascertained from Swedish national registers. Parent-offspring resemblance was calculated by tetrachoric correlation.

Results: In Swedes born from 1960 to 1995, prevalence rates of AUD were stable while DUD rates increased substantially. Best-estimate tetrachoric correlations (±95% confidence intervals) between AUD in biological parents and AUD and DUD in their offspring were, respectively, +0.19 (0.18-0.20) and +0.18 (0.17-0.20). Parallel results from DUD in parents to AUD and DUD in children were +0.12 (0.10-0.13) and +0.27 (0.26-0.28). When divided into older and younger cohorts, the specificity of DUD transmission increased substantially over time, while the genetic correlation between AUD and DUD significantly decreased.

Conclusions: Raised when alcohol was the preferred substance of abuse and illicit drugs highly stigmatized, AUD in parents reflected a general liability to substance use disorders, as they transmitted similar genetic risk for AUD and DUD to their children raised when both substances were widely available and relatively acceptable. DUD in parents, by contrast, reflected a more specific liability to DUD and, when transmitted to offspring, produced a considerably stronger risk for DUD than for AUD that increased over time. The magnitude and specificity of the genetic liability to psychoactive substances can be influenced by the availability of that substance.