The subjective responses to amphetamine and the risk for amphetamine dependence are heritable traits [1], [2], [3]. It is hypothesized that the genetic variation underlying subjective drug responses may contribute to the risk of developing drug dependence [4], [5], [6], [7], [8], [9]. Previous genetic association studies of the response to amphetamine suggest a role for genetic sources of variability in acute drug effects, but have focused on candidate genes [1], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Candidate gene studies are inherently limited in their ability to generate novel hypotheses compared with genome-wide association studies (GWAS). Here we report the results of the first GWAS for subjective response to acute administration of a drug of abuse in humans, using a laboratory-based, double-blind, placebo-controlled, within-subjects design to quantify subjective response to d-amphetamine in 381 healthy non-drug abusing participants, and testing for associations with 5.4 million (typed and imputed) single nucleotide polymorphisms (SNPs) across the genome.
