overwhelming majority of the European-American participants who were followed did consent to participation in genetic studies, potential contributions that the non-consenting individuals might have made to the present results remain unknown. 6) The pooling approach that we use here provides excellent correlations between individually-genotyped and pooled allele frequency assessments in validation experiments. This approach has allowed us to use these samples without adding additional confidentiality burdens to these intensively-studied individuals. Nevertheless, estimates of allele frequencies based on pooled data represent approximations of "true" allele frequency differences that might be determined by error free individual genotyping of each participant. 7) There is no indication that the overall positive results reported here are based on the SNPs whose assays provide more noise, and no indication that occult stratification on racial/ethnic lines contributed overall to the results that we obtain here. However, we cannot totally exclude contributions of occult stratification that cannot be detected by these overall screens to findings in specific genes. 8) The convergent data derived from studies of individuals with dependence on substances in several different pharmacological classes supports the idea that many allelic variants enhance vulnerability to dependence on a number of substances. These results do not exclude additional
