The relationship between genetic influences on alcohol dependence and on patterns of alcohol consumption

Abstract

Background: Genetic factors impact substantially both on alcohol consumption (AC) and on the risk for alcohol dependence (AD). However, we know little about the degree to which measures of AC index the genetic risk for AD.

Methods: We assessed a lifetime history of AD by DSM-IV criteria and four measures of AC at the time of heaviest drinking (drink frequency, regular quantity, maximum quantity, and drunk frequency) in 5,073 adult twins from same-sex pairs from the Virginia Twin Registry. Structural models were fitted using Mx.

Results: We found evidence for different genetic structure in the sexes. In women, genetic risk for AD and for the four measures of AC was entirely shared. In men, the AC measures captured 85% of the genetic risk for AD. In women, the genetic relationship with AD was strongest for drunk frequency and in men for both drunk frequency and regular quantity.

Conclusions: In a population-based sample of twins, four relatively simple measures of AC obtained for the time of lifetime heaviest drinking were able to capture all (in women) or a very large proportion (in men) of the genetic risk for the complex multi-dimensional construct of AD. If replicated, these results have practical implications for studies aiming to assess genetic risk for AD.

Fig. 1

(A) Our full structural model relating genetic risk for alcohol dependence (AD) and four measures of alcohol consumption (AC). The model contains seven separable sources of genetic risk, two of which (A1 and A2) are common factors and five of which (A3 through A7) are specific to AD and the 4 forms of AC. The first common factor—A1—influences both AD and the forms of AC. Critically, the second common factor—A2—influences only the 4 forms of AC. (B) The full model depicted in Fig. 1A with the deletion of factor A1. This model represents the hypothesis that genetic risk factors for AD and AC are unrelated. (C) The full model depicted in Fig. 1A with the deletion of factor A2. This model represents the hypothesis that all the genetic risk factors shared among AD and the AC measures can be explained by one common factor. However, specific genetic risk for each measure is permitted in the model through factors A3 to A7. (D) The full model depicted in Fig. 1A with the deletion of factors A2 and A3. This model evaluates the hypothesis that all the genetic risk for AD is shared with the genetic risk common to the AC measures.

Fig. 2

Parameter estimates from the best-fit model for alcohol dependence and four measures of alcohol consumption in female–female twins. The parameter estimates depicted (along with their standard errors) are factor loadings and are squared to obtain proportions of variance.

Fig. 3

The best-fit model for alcohol dependence with standard errors and four measures of alcohol consumption in male–male twins.