The Collaborative Study on the Genetics of Alcoholism (COGA) is a National Institutes of Health-sponsored project aimed at identifying genes that contribute to alcohol-related outcomes. In COGA, we have conducted a series of analyses aimed at understanding the underlying genetic architecture of alcohol dependence (Zlojutro et al., 2011). Here, we couple this knowledge with a clinical evaluation of the information captured by currently available genetic information in risk prediction for alcohol dependence. COGA has previously reported positive family-based association results for AD using a high-density family sample. Many of these genes have also been associated with AD in other studies (Table 1). We created additive genetic sum scores based on risk alleles of associated SNPs in these genes. We then compared the sum score with family history in its ability to discriminate between cases and controls for AD in a subset of the COGA sample that is independent of the gene-finding family sample and in a subset of independent individuals in the Study of Addiction: Genes and Environment (SAGE) genome-wide association study (GWAS) sample. Finally, we explored the clinical validity of results from genome-wide association analyses.
