CAGE criteria were used in the NTR sample. A fourth limitation may be that specific genetic effects on AD may be harder to detect as it is much more likely to be comorbid with ND than vice versa. For instance in our general population Australian sample in ever smokers 32% of ND cases have a history of AD, whereas 56% of our AD cases have a history of ND. Also the small number of comorbid cases available within the Dutch samples precluded the comorbid AD+ND+ vs AD-ND- analysis in those samples. A final feature, which could be considered either a strength or a limitation, is recruitment of subjects from the general population rather than a clinical source. The severity of dependence may well be less among a population-based sample, but most alcohol-related problems occur in the large number of people who are only moderately affected; and smoking is also a problem affecting the general community. It should also be noted that this is a study of alcohol and nicotine dependency versus non-dependency. As such, we did not use a group of hypercontrols, but rather allowed AD and ND controls to represent the general population. This is similar to many other
