Subjects were members of families in which at least three first-degree relatives were alcohol dependent [meeting both DSM-IIIR lifetime criteria for alcohol dependence (24) and Feighner criteria for definite alcohol dependence (25)]. Only non-Hispanic families of European American descent (219 families) were analyzed. The ascertainment and assessment have previously been described (26,27) and are available in detail at zork.wustl.edu/niaaa/coga_instruments/resources.html. A genetically informative subset of families was selected as described in more detail by Foroud et al. (27). Subjects were collected at six centers in the USA: Indiana University, State University of New York Health Science Center, University of Connecticut, University of Iowa, University of California/San Diego and Washington University, St Louis. The institutional review boards of all participating institutions approved the study. Probands were identified through alcoholism treatment programs, and after providing written informed consent, probands and their relatives were administered a validated poly-diagnostic instrument, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview (28,29).