Initially, case–control studies often were performed using small numbers of alcoholic and control subjects and examined the role of a single gene, frequently testing only for a single variation. This approach has limited power, and many results could not be replicated. The most robust result from these early studies was the demonstration that the genes encoding two alcohol-metabolizing enzymes—alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)—played an important role in determining alcoholism risk (this will be discussed in more detail in the next section).