The primary phenotype in this study was diagnosis of DSM-IV AD29. Individuals meeting criteria for DSM-IV AD at age 15 or older were coded as affected. Individuals were coded as unaffected if they met all of the following criteria: 1) ≥ 21 years; 2) endorsed < 2 criteria for DSM-IV dependence or abuse for alcohol, and 3) endorsed < 2 criteria for DSM-IV dependence or abuse for cocaine, opioids, marijuana, sedatives, and stimulants. Affected individuals <15 years of age and unaffected individuals <21 years of age were excluded. Exclusions for age removed affected individuals with early onset AD who might be etiologically distinct, due to the potentially stronger role of environmental than genetic influences 30. For unaffected individuals, exclusion of those < 21 years of age removed those who may not have passed through the peak period of risk for the onset of AD 31,32. Due to the strong evidence for shared genetic influences on alcohol and other forms of substance use disorders, individuals who did not meet criteria for AD but endorsed multiple abuse or dependence criteria for other substances were also excluded from the analysis.
