The most commonly used definitions of alcohol dependence are delineated in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994) (DSM-IV) and International Classification of Disease and Related Health Problems, 10th edition (World Health Organization, 1992) (ICD-10), which require endorsement of 3 out of 6 to 7 symptom groups. Importantly, this allows two individuals with non-overlapping symptoms to meet criteria for alcohol dependence and can result in significant phenotypic heterogeneity. It is likely that such heterogeneity is responsible in part for the difficulties in detecting susceptibility loci for alcohol dependence. Notably, Prescott and colleagues (2006) utilized an approach to linkage with the potential to explain such heterogeneity. Specifically, they evaluated which alcohol dependence symptoms were contributing to the each of the linkage signals reported in their sample. For example, they noted that the symptoms of tolerance, binge drinking, and inability to quit drinking provided the strongest contributions to an observed linkage peak on chromosome 4.
