The last dozen or so years have seen a huge revision in our understanding of alcohol dependence genetics. Notwithstanding the long-known relationship of the alcohol metabolizing enzymes to AD risk in some Asian populations, the first linkage studies were initially viewed as disappointing, because they failed to provide genomewide significant results. But in the years since, the alcohol metabolizing enzyme findings have been replicated across many genes and populations beyond the initial work, and additional replicable risk loci have been identified. Only a fraction of the genetic risk is yet accounted for by known loci, but the growing number of replicable loci is encouraging. Similarly encouraging are the facts that these loci coincide with protein products that could be related to AD risk and that they were identified by the application of standard methods. Admittedly, though, proof that a specific variant is related to disease risk must be based on studies that take into account the function of allelic variants—statistical evidence from linkage and association in not sufficient.
