Consistency with Hardy-Weinberg equilibrium expectations for each SNP was examined with the χ2 test in each discovery sample, using a set of unrelated subjects without CD (1 random unaffected subject from each family), and in each of the control groups from the replication sample. Two SNPs (rs9400554 and rs6937479) with significant evidence of deviation from Hardy-Weinberg equilibrium (P>.001) in the AA replication sample were excluded from analyses of allelic and genotypic association in that data set. In the family samples, mendelian inheritance of all genotypes was evaluated using PedCheck,29 and pairwise marker linkage disequilibrium was examined using the Haploview program, version 4.0.30 Association of the MANEA SNPs with CD and CIP in the family samples was evaluated using the FBAT program,31 assuming an additive model under the null hypothesis of no linkage and no association. Allele frequencies were estimated by FBAT using the expectation-maximum algorithm. In the case-control samples, a χ2 test was used to examine the association of SNP alleles and genotypes with cocaine-related traits. Odds ratios and their 95% confidence intervals for the allelic associations were computed using