This lack of replication across methods reflects two distinct issues in these different studies designs: the low threshold for significance in candidate gene studies results in a high false positive rate, and the high threshold for significance in the GWAS design leads to a low sensitivity to detect true genetic contributions to disease. While candidate gene studies of addiction should therefore be interpreted with caution, they should not be dismissed because they may have captured unique phenotypes that allowed the detection of genetic variation that will not be seen in the large scale heterogeneous GWAS. Regardless, validation of human genetic mutations linked to illicit drug use awaits further study.
