Our findings indicated that AFD is not specifically associated with alcoholism but rather is correlated with a broad range of indicators of disinhibited behavior and psychopathology. Moreover, individuals who first drink at a relatively early age manifest elevated rates of disinhibitory behavior and psychopathology before they first try alcohol. Taken together, these findings suggest that the association of AFD with alcoholism reflects, at least in part, a common underlying vulnerability to disinhibitory behavior. Whether an early AFD directly influences risk of adult alcoholism remains unclear.

Our findings indicated that AFD is not specifically associated with alcoholism but rather is correlated with a broad range of indicators of disinhibited behavior and psychopathology. Moreover, individuals who first drink at a relatively early age manifest elevated rates of disinhibitory behavior and psychopathology before they first try alcohol. Taken together, these findings suggest that the association of AFD with alcoholism reflects, at least in part, a common underlying vulnerability to disinhibitory behavior. Whether an early AFD directly influences risk of adult alcoholism remains unclear.

We report results from a genome wide association study (GWAS) of five quantitative indicators of behavioral disinhibition: Nicotine, Alcohol Consumption, Alcohol Dependence, Illicit Drugs, and non-substance related Behavioral Disinhibition. The sample, consisting of 7188 Caucasian individuals clustered in 2300 nuclear families, was genotyped on over 520,000 SNP markers from Illumina’s Human 660W-Quad Array. Analysis of individual SNP associations revealed only one marker-component phenotype association, between rs1868152 and Illicit Drugs, with a p-value below the standard genome-wide threshold of 5 × 10-8. Because we had analyzed five separate phenotypes, we do not consider this single association to be significant. However, we report 13 SNPs that were associated at p < 10-5 for one phenotype and p < 10-3 for at least one other phenotype, which are potential candidates for future investigations of variants associated with general behavioral disinhibition. Biometric analysis of the twin and family data yielded estimates of additive heritability for the component phenotypes ranging from 49% to 70%, GCTA estimates of heritability for the same phenotypes ranged from 8% to 37%. Consequently, even though the common variants genotyped on the GWAS array appear in aggregate to account for a sizable proportion of heritable effects in multiple indicators of behavioral disinhibition, our data suggest that most of the additive heritability remains “missing”.

In contrast to findings in some adult samples, personality characteristics associated with a family history of substance use disorders are found even in adolescent offspring who have not yet developed these disorders themselves, suggesting that personality might be one indicator of familial risk for substance use disorders during this developmental stage. Personality profiles of offspring of parents with substance use disorders also show some diagnostic specificity, with constraint associated with parental drug abuse and negative emotionality with parental alcoholism.

No abstract