We did not find additional support in the SAGE sample. This may be due to several factors. First, the power to replicate findings of relatively small effect, such as those identified in this sample, is modest in replication samples of the size of SAGE. Second, the COGA family GWAS sample is quite unique in that the families were selected because of their large size and density of AD. Much of the SAGE sample consists of individuals recruited for nicotine and cocaine, then selected for comorbid AD. The risk factors contributing to AD and our AD-related phenotypes may be different from those more commonly found in sporadic AD or AD associated with other substance dependence. Finally, the lack of replication may be that our initial COGA findings are false positive associations. Clearly, further studies, ideally in family samples ascertained for a high level of AD, are necessary.
