CD is understudied, particularly in relation to the extent of the individual and societal problems it causes. Animal studies have begun to elucidate the biological substrates of CD (e.g., ref. 2), but this has not been accompanied by comparable elucidation of the sources of the genetic contribution to this trait. CD has a heritability of about 0.65 in females3 and 0.79 in males4, so the potential exists to identify specific genetic variants that underlie disease risk. There have been numerous candidate gene association studies of CD and related traits, and several genomewide linkage studies, the latter identifying chromosomal regions likely to harbor risk-influencing genes.5–6 Genomewide association studies (GWAS), when adequately powered, have generally been successful at identifying genes responsible for some of the risk for most complex traits for which they have been employed. However, no GWAS for CD has been published to date. To our knowledge, the only other GWAS for an illegal substance dependence (SD) diagnosis with genomewide-significant (GWS) results is our investigation of opioid dependence (OD).7 A previous GWAS of cannabis dependence8 did not report GWS results.
