Drug addiction is a devastating and highly complex neurobiological phenomenon. It is associated with numerous risk factors, and presents with multiple stages and behaviors that have proven difficult to study alone and in combination. The Center for Systems Neurogenetics of Addiction combines the expertise of neuroscientists, epidemiologists, geneticists and computational scientists in an unprecedented approach to understanding the biological mechanisms behind individual risk of addiction. It takes advantage of recent advances in precise genetic, genomic and behavioral analysis in the laboratory mouse. Despite extensive evidence that addiction is a disease with variable individual risk, there remains a widespread misconception that addiction is a moral failing and one that is completely under the control of the individual. A main Center goal is thus to find new ways to prevent addiction in people at risk, and intervene in those already addicted. We aim to identify ways in which some individuals are more likely than others to start using or become addicted to illicit substances, and to improve our understanding of how the brain responds in terms of compulsive behavior. Deploying state-of-the-art behavioral and diagnostic tools, researchers will evaluate extreme genetic and physiological variation in the Diversity Outbred Mouse Population in search of traits that predispose individuals to addiction. Sample target traits include impulsivity, sensitized drug response, reward-seeking behavior, adolescent nicotine exposure and circadian variation. They will then correlate these traits with murine genomes to build datasets, graphs and other combinatorial structures for use in unraveling mechanisms of addiction and extending putative findings from mouse to human. These resources and tools will be available to the global research community. The Center will also develop and share new mouse models of addiction susceptibility based on the mechanisms they discover.