Genome-wide association for methamphetamine dependence: Convergent results from 2 samples

Context: We can improve understanding of human methamphetamine dependence, and possibly our abilities to prevent and treat this devastating disorder, by identifying genes whose allelic variants predispose to methamphetamine dependence. Objective: To find "methamphetamine dependence" genes identified by each of 2 genome-wide association (GWA) studies of independent samples of methamphetamine-dependent individuals and matched controls. Design: Replicated GWA results in each of 2 casecontrol studies. Setting: Japan and Taiwan. Participants: Individuals with methamphetamine dependence and matched control subjects free from psychiatric, substance abuse, or substance dependence diagnoses (N=580). Main Outcome Measures: "Methamphetamine dependence" genes that were reproducibly identified by clusters of nominally positive single-nucleotide polymorphisms (SNPs) in both samples in ways that were unlikely to represent chance observations, based on Monte Carlo simulations that corrected for multiple comparisons, and subsets of "methamphetamine dependence" genes that were also identified by GWA studies of dependence on other addictive substances, success in quitting smoking, and memory. Results: Genes identified by clustered nominally positive SNPs from both samples were unlikely to represent chance observations (Monte Carlo P