provide a more accurate estimate of the phenotype, as dichotomizing variables can cause a loss of information. Moreover, our incorporation of both AAD symptoms is unique. This study, however, is not without limitations. Specifically, there is low power to detect and replicate genetic associations when the CADD and GADD samples are analyzed separately, a fact that could explain false positives. In addition, there might exist unidentified ascertainment or sample characteristics differences between the CADD and GADD samples, again leading to inconsistent results. High comorbid drug use is also present in our samples, which could confound results. Although we attempted to capture all the genetic signals in the region, some may have been missed. Furthermore, it is becoming clear that the genetic risk for alcohol disorders is likely due to common variants in many genes, each of small effect, as well as rare variants with potentially large effects (Enoch 2013). The advent of next generation sequencing methods may allow identification of novel rare variants in future studies.
