Kendler · Psychological medicine 2023 · Family-based registry cohort study · n=?

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

Level 3 - non-randomized controlled study

Nationwide non-randomized family-based registry cohort study using parent-offspring designs

PubMed 35993335 · doi:10.1017/S0033291722002549 · record verified 2026-08-26

What was done

Using Swedish national registers, researchers examined biological parents and their offspring born between 1960 and 1995 across three family configurations: not-lived-with biological fathers, not-lived-with biological mothers, and adoptive families. Diagnoses of alcohol use disorder (AUD) and drug use disorder (DUD) were ascertained, and cross-generational parent-offspring resemblance was evaluated using tetrachoric correlations across birth cohorts to test whether substance availability moderated the specificity of genetic transmission.

What was found

Across the 1960–1995 birth cohorts, AUD prevalence remained stable while DUD prevalence rose substantially. Tetrachoric correlations (95% CI) between parental AUD and offspring outcomes were +0.19 (0.18–0.20) for offspring AUD and +0.18 (0.17–0.20) for offspring DUD. Parental DUD showed correlations of +0.12 (0.10–0.13) with offspring AUD and +0.27 (0.26–0.28) with offspring DUD. In younger cohorts, the specificity of DUD transmission increased substantially while the genetic correlation between AUD and DUD decreased significantly.

Why it matters

These findings indicate that genetic liability to substance use disorders is not fixed in its presentation; environmental factors like historical substance availability and social acceptability influence whether genetic risk manifests broadly or specifically for a particular drug.

Limits

The abstract does not state the exact sample size. Diagnoses were derived from medical and administrative registers, which likely capture more severe presentations and undercount subclinical substance misuse. Findings from the Swedish population may not generalize to settings with different drug policies, healthcare systems, or cultural norms around substance use.