Evidence for multiple genetic factors underlying the DSM-IV criteria for alcohol dependence.

To determine the number of genetic factors underlying the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for alcohol dependence (AD), we conducted structural equation twin modeling for seven AD criteria, plus two summary screening questions, in 7133 personally interviewed male and female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, who reported lifetime alcohol consumption. The best-fit twin model required three genetic and two unique environmental common factors, and criterion-specific unique environmental factors. The first genetic factor was defined by high loadings for the probe question about quantity and frequency of alcohol consumption, and tolerance criterion. The second genetic factor loaded strongly on the probe question about self-recognition of alcohol-related problems and AD criteria for loss of control, desire to quit, preoccupation and activities given up. The third genetic factor had high loadings for withdrawal and continued use despite the problems criteria. Genetic factor scores derived from these three factors differentially predicted patterns of comorbidity, educational status and other historical/clinical features of AD. The DSM-IV syndrome of AD does not reflect a single dimension of genetic liability, rather, these criteria reflect three underlying dimensions that index risk for: (i) tolerance and heavy use; (ii) loss of control with alcohol associated social dysfunction and (iii) withdrawal and continued use despite problems. While tentative and in need of replication, these results, consistent with the rodent literature, were validated by examining predictions of the genetic factor scores and have implications for gene-finding efforts in AD.