Very little work of genome-wide scope has been accomplished for cocaine dependence or for other stimulants; all cocaine-related work has relied primarily on the Yale–Penn cohort. The first46 of the two available GWAS identified several risk variants (e.g., family with sequence similarity 53, member B (FAM53B)) that despite the years since the completion of the study, still await not only replication, but any suitably powered replication attempt. On the other hand, the FAM53B locus has seen replication of sorts in an animal model47. The second study48, which incorporated data used in the first together with additional cohorts, did not identify GWS risk loci but showed consistent genetic overlap of cocaine dependence with other psychiatric disorders and behavioural traits. Another analysis of the Yale–Penn data showed that phenotypic heterogeneity and gene–environment interplay affect gene discovery (e.g., transmembrane protein 51 (TMEM51)) in cocaine use disorder49. Despite the morbidity and mortality associated with these traits, they are not common enough to be approachable through biobank data so far, and there is regional variation (cocaine use is more predominant in some parts of the US, whereas methamphetamine use is more common in others) tending to increase heterogeneity.
