While the above represents a data-driven approach for assignment of SNPs to genes/systems, other methods allow investigators to ascribe SNPs to a gene set and conduct set-based association tests. Using such an approach, one study linked variants in the norepinephrine, glutamatergic, GABAergic, and corticotropin-releasing hormone systems to alcohol dependence (Reimers, Riley, Kalsi, Kertes, & Kendler, 2012). The present study uses a similar approach to examine the relationship between all SNPs in genes within the endocannabinoid system and cannabis dependence. Due to the relatively recent characterization of cannabinoids' actions in the brain and the limited exploration of individual SNPs in this system, prior robust association findings are limited, making system-level and gene-based analyses an appealing alternative to traditional single-SNP or additive multilocus candidate gene approaches (e.g., Nikolova, Ferrell, Manuck, & Hariri, 2011).
