It is also important to keep a number of limitations in mind in considering the present results. 1) The preplanned approach used here demands that multiple nominally-positive SNPs from each sample tag the same genomic region that lies within a gene. Requirements that nominally positive SNPs from the current dataset come from each of the two 500 k array types add a technical control. Monte Carlo approaches that do not require specification of underlying distributions can readily judge the degree to which all of the observations made here could be due to chance. Nevertheless, there have been no unanimous criteria for declaring "replication" or "convergence" for GWA studies, a consideration worth considering in evaluating the current results. 2) The ECA samples are of modest size, limited by the numbers of substance abusing or dependent individuals in the aging Baltimore ECA cohort follow-up samples. Power calculations that document the modest power in European-Americans samples revealed even more modest power for the smaller number of African-American substance dependent individuals in this sample; we have thus not analyzed these samples. Modest power limits
