In the present study, we modeled the genetic architecture of the alcohol outcomes available in the Finntwin16 sample in an attempt to examine more genetically homogenous alcohol phenotypes. We found modest evidence of association between DRD2/ANKK1 SNPs and both genetically informed measures of alcohol consumption and problems. As rs10891549 and rs1554929 are highly correlated (r2=.98) and rs6275 and rs6279 are highly correlated (r2=0.87), there were two true independent signals detected in this sample. The first of these signals (rs10891549/rs1554929) is highly correlated with the SNPs within the ANKK1 gene, and may be indirectly associated with ANKK1, the original locus detected in association with alcohol problems. The association between the rs10891549/rs1554929 locus was found with both general alcohol consumption and problems in this sample. The second signal (rs6275/rs6279) may be potentially functional as rs6275 and rs6279 are non-synonymous polymorphisms that are located on the 3′UTR and may have a regulatory effect. This locus was only significantly associated with alcohol problems in the Finntwin16. Perhaps multiple independent signals within the DRD2/ANKK1 gene complex are differentially associated with alcohol outcomes; this may provide some explanation of the inconsistent genetic association findings.
