The moderation of the genetic risk for alcohol and drug use disorders in a Swedish national sample by the genetic aptitude for educational attainment

Background Does the genetic aptitude for educational attainment (GAEA) moderate the genetic risk for alcohol use disorder (AUD) and drug use disorder (DUD)? Methods In the native Swedish population, born 1960-1980 and followed through 2017 (n = 1 862 435), the family genetic risk score (FGRS) for AUD and DUD and GAEA were calculated from, respectively, the educational attainment and risk for AUD and DUD, of 1st through 5th degree relatives from Swedish national registers. Analyses utilized Aalen's linear hazards models. Results Risk for AUD was robustly predicted by the main effects of FGRS(AUD) [b = 6.32 (95% CI 6.21-6.43), z = 64.9, p < 0.001) and GAEA [b = -2.90 (2.83-2.97), z = 44.1, p < 0.001] and their interaction [b = -1.93 (1.83-2.03), z = 32.9, p < 0.001]. Results were similar for the prediction of DUD by the main effects of FGRS(DUD) [b = 4.65 (CI 4.56-4.74), z = 59.4, p < 0.001] and GAEA [-2.08 (2.03-2.13), z = 46.4, p < 0.001] and their interaction [b = -1.58 (1.50-1.66)), z = 30.2, p < 0.001]. The magnitude of the interactions between GAEA and FGRS(AUD) and FGRS(DUD) in the prediction of, respectively, AUD and DUD was attenuated only slightly by the addition of educational attainment to the model. Conclusions and relevance The genetic propensity to high educational attainment robustly moderates the genetic risk for both AUD and DUD such that the impact of the genetic liability to AUD and DUD on the risk of illness is substantially attenuated in those with high v. low GAEA. This effect is not appreciably mediated by the actual level of educational attainment. These naturalistic findings could form the basis of prevention efforts in high-risk youth.