The present study utilizes GRS generated from the analysis of AO-AD in COGA (discovery sample) conducted by Kapoor et al.15 and applies these scores to two independent samples, the Study of Addictions Genes and Environment (SAGE; using the portion independent of the COGA subjects who were in the discovery sample)17 and a sample of Australian subjects (OZ-ALC).18 In contrast to COGA, which is comprised of extended pedigrees with a high rates of alcohol dependence, SAGE consisted of alcohol-dependent cases and alcohol exposed but non-dependent controls. Even though SAGE subjects were drawn from studies that used family history of alcohol and drug dependence to ascertain cases, including COGA, all overlapping subjects were removed and all subjects were unrelated to each other. OZ-ALC, on the other hand, consisted of pedigrees that were derived from various sources, including family studies ascertained for heavy drinking and heavy smoking and a sample consisting of large sibships. Despite being similar to COGA for sibship size, the density of alcohol-related problems in the OZ-ALC pedigrees is substantially lower. The variability in SAGE and OZ-ALC allowed us to investigate the generalizability of the COGA findings.
