The power to identify genes contributing to the risk for disease may be increased through the analysis of quantitative endophenotypes highly correlated with that disorder but measurable in all individuals. Rather than focus on the presence or absence of AD, we used the number of AD symptoms as our primary phenotype. Some research has indicated that AD may be better captured with a symptom count rather than with a dichotomous diagnosis19–21. Evidence from twin studies has shown that two quantitative measures, dependence symptoms and alcohol consumption are highly correlated with alcohol dependence and index closely the risk for alcohol dependence22,23. Symptom counts can be computed for any drinker, including older adolescents who are just beginning to use alcohol but may not fulfill criteria for AD, thus allowing us to use more of our sample in the analysis and increase the power to detect association. Since most other studies on alcoholism have used a dichotomous diagnosis, DSM-IV alcohol dependence, we analyzed the regions of interest identified in the symptom count analysis to evaluate if similar findings emerge.
