Deep Sequencing Studies for Cannabis and Stimulant Dependence

Cannabis and stimulants are among the most widely used illicit drug in the United States, and their use is associated with substantial physical and psychiatric sequelae. Twin studies have shown a substantial genetic component to the etiology of cannabis and stimulant use disorders, but, genome-wide association studies using genotype data obtained from microarrays have yielded few robust results. The advent of increasingly economical whole genome sequencing provides new opportunities to identify trait-associated sequence variations. The present study proposes to identify sequence variants that affect stimulant and cannabis dependence in three cohorts. The three study cohorts were ascertained as part of the Mission Indian Study (PI Cindy Ehlers), the combined Yale-University of Connecticut Addiction Study samples (PI Joel Gelernter) and the San Francisco Family Study (PI Kirk Wilhelmsen). Because three populations with different continental origins were studied, the present study will also ascertain whether the major genetic risk factors for the traits of interest are shared or population-specific. ]]>
UCSF Family Study Sample: Probands in the UCSF Family Study were recruited nationwide for a study of alcoholism and other substance dependence. Inclusion criteria for probands required that they meet screening criteria for a lifetime alcohol dependence diagnosis and have at least one sibling or both parents available to participate. Exclusion criteria for probands required that they did not meet criteria for serious drug addictions other than cannabis (e.g., stimulants, cocaine, or opiates) or have a history of intravenous substance use. Additional exclusion criteria for probands included a current or past diagnosis involving psychotic symptoms, a life-threatening illness, or an inability to speak and read English. If the proband was deemed eligible to participate, their relatives were then contacted via mail and invitated to participate in the study. ]]>