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The GEDI will support research using existing research samples to investigate main effects, correlations , and interactions among genetic, environmental , and developmental factors in the etiology of substance abuse and related phenotypes in humans. The term "substance abuse" as used in this RFA refers broadly to several different but related concepts including substance use (quantity, frequency, patterns , trajectories) and substance abuse and dependence as defined by diagnostic criteria. While it is recognized that these concepts may not be interchangeable , the term " substance abuse " is used for the purposes of fluency. The term " substance " refers primarily to nicotine, alcohol, cannabis, cocaine, stimulants, and opiates, but also includes the entire range of licit and illicit substances of potential addiction. The term " related phenotypes " refers to constructs that have been shown empirically to convey risk for substance abuse, such as behavioral disinhibi-tion. " Developmental research " refers to the study of progressive change that occurs as humans move through the lifecourse. The National Institute on Mental Health (NIMH) has an interest in applications where the research contributes to knowledge about the interplay of genetic, environmental, and developmental factors in the etiology of adverse outcomes; however, no funds will be committed at this time. Prior lines of research have established that genetic, environmental, and developmental factors all contribute to vulnerability to substance abuse and related phenotypes. Both animal and human studies have demonstrated genetic influences on substance abuse, with heritability estimates ranging from 40 to 60%, and promising candidate loci and genes for substance abuse have been identified. Genetic influences have also been shown for many related phenotypes, and some (e.g., externalizing disorders) share genetic factors with substance abuse. As with other complex disorders, it is likely that multiple genes of small effects contribute to vulnerability to substance abuse and related phenotypes, and that environmental conditions moderate genetic influence. A wide variety of environmental variables have been correlated with substance abuse and related phenotypes, including in utero exposures, parenting, trauma and stress, peer influences and/or neighborhood and societal factors. Many of these correlations have been very strong and frequently replicated, forming the basis for numerous preventive intervention studies with youth at high risk due to individual and familial factors in combination with the social context over the course of development. The role of developmental factors is highlighted not only by the fact that the human …