Evidence for an interaction between age at first drink and genetic influences on DSM-IV alcohol dependence symptoms

Abstract

Background: Research suggests that individuals who start drinking at an early age are more likely to subsequently develop alcohol dependence. Twin studies have demonstrated that the liability to age at first drink and to alcohol dependence are influenced by common genetic and environmental factors, however, age at first drink may also environmentally mediate increased risk for alcohol dependence. In this study, we examine whether age at first drink moderates genetic and environmental influences, via gene x environment interactions, on DSM-IV alcohol dependence symptoms.

Methods: Using data on 6,257 adult monozygotic and dizygotic male and female twins from Australia, we examined the extent to which age at first drink (i) increased mean alcohol dependence symptoms and (ii) whether the magnitude of additive genetic, shared, and nonshared environmental influences on alcohol dependence symptoms varied as a function of decreasing age. Twin models were fitted in Mx.

Results: Risk for alcohol dependence symptoms increased with decreasing age at first drink. Heritable influences on alcohol dependence symptoms were considerably larger in those who reported an age at first drink prior to 13 years of age. In those with later onset of alcohol use, variance in alcohol dependence was largely attributable to nonshared environmental variance (and measurement error). This evidence for unmeasured gene x measured environment interaction persisted even when controlling for the genetic influences that overlapped between age at first drink and alcohol dependence symptoms.

Conclusions: Early age at first drink may facilitate the expression of genes associated with vulnerability to alcohol dependence symptoms. This is important to consider, not only from a public health standpoint, but also in future genomic studies of alcohol dependence.

Figure 1

Decreasing hazards of endorsing one or more DSM-IV alcohol dependence symptoms (survival = endorsed 1+ alcohol dependence symptom) with increasing age at 1^st drink.

Figure 2

Moderation of variance and of additive genetic (a2), shared environmental (c2) and non-shared environmental (e2) influences in women. The upper panel shows change in total variance and in the A, C and E components by age at first drink – in this upper panel, the variance curve, at any point, reflects the sum of the unstandardized A, C an E.

Figure 3

Moderation of variance and of additive genetic (a2), shared environmental (c2) and non-shared environmental (e2) influences in men. The upper panel shows change in total variance and in the A, C and E components by age at first drink – in this upper panel, the variance curve, at any point, reflects the sum of the unstandardized A, C an E. The lower panel shows change in A, C and E when they are standardized such that: (a+x*moderator)²+(c+y*moderator)²+(e+z*moderator)²=1.0, i.e. the variance is set to 1.0. Now, the change in A reflects moderation of heritable factors.