Interestingly, the variant that was initially proposed to be associated to alcoholism has been shown to map within the adjacent gene, ANKK1 (Neville et al. 2004). DRD2 maps close to three other genes, in the order NCAM1/TTC12/ANKK1/DRD2. Based on the premise that observed weak and inconsistent DRD2 association signals might be better explained through LD with another gene in this cluster (our initial hypothesis was that this might be the NCAM1 gene), we studied a set of 43 SNPs spanning this region. In our initial article (Gelernter et al. 2006), where the subjects were drawn from a cocaine and opioid dependence linkage sample, we found very strong evidence of association of ND with SNPs that map to a haplotype block that includes markers from ANKK1 and TTC12. This region coincides with a linkage peak we observed for ND (Gelernter et al. 2006, 2007). We have since found similar evidence for association of AD to markers in the same haplotype block in a completely independent sample; in this case, the associated region centers on two TTC12 SNPs (Yang et al. 2007).
