Our results are broadly consistent with a literature38–47 in which, led by the efforts of Gelernter, Kranzler, and colleagues, attention has shifted from DRD2 to ANKK1 and TTC12 as the genes in this region most strongly associated with substance dependence. They initially conducted a family-based association study38 of tobacco dependence in a largely polysubstance-dependent sample drawn from sets of European American (EA) and African American (AA) affected (cocaine or opioid dependent) sibling pairs. The strongest association in pooled African American and European American data included ANKK1 and TTC12 SNPs in a moderate to high LD block that overlaps our main findings [e.g., their top hits included rs4938012 (p=8 × 10−6) and rs4938013 (p=3 × 10−5)]. Of note, DSM-IV nicotine dependence is more highly correlated with other DSM-IV substance dependence diagnoses than is Fagerström score (for which they found much weaker association). Further analyses implicated a 4-SNP haplotype spanning TTC12 and ANKK1. They later focused40 on alcohol dependence in two European American samples, finding only nominally significant associations for individual SNPs; haplotype-based analyses observed significant associations centering on TTC12, NCAM1, and
