Despite twin studies showing that 50–70% of variation in DSM-IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to cannabis dependence. We conducted a genome-wide association study of DSM-IV cannabis dependence. Association analyses of 708 DSM-IV cannabis-dependent cases with 2346 cannabis-exposed non-dependent controls was conducted using logistic regression in PLINK. None of the 948 142 single nucleotide polymorphisms met genome-wide significance (P at E–8). The lowest P values were obtained for polymorphisms on chromosome 17 (rs1019238 and rs1431318, P values at E–7) in the ANKFN1 gene. While replication is required, this study represents an important first step toward clarifying the biological underpinnings of cannabis dependence.