Many of these studies, when producing positive results, did so by assessing multiple markers in multiple ways, and although correcting for the number of comparisons within an analysis, performed multiple analyses, so at best, most results are “nominally” significant. In many instances, allelic variants were more strongly associated with particular drug related phenotypes (Comings, et al., 1994; Gorwood, et al., 2003; Ide, Kobayashi, et al., 2004; Sander, Harms, Lesch, et al., 1997; Shi, et al., 2002), including preference for, or dependence on, particular drug classes (Comings, Gonzalez, et al., 1999; Persico, et al., 1996a), or degree of drug preference (Persico, Bird, Gabbay, & Uhl, 1996b), often when the overall association with drug dependence was not significant. In the Comings et al. (1999) study the dopamine D3 receptor (DRD3) was found to be associated with cocaine dependence, but not dependence on amphetamines, opiates or alcohol. More recently, responses to bupropion in nicotine cessation trials have been associated with the dopamine D4 receptor (DRD4) (Leventhal, et al., 2012). Additionally, the apparent effects in some studies have been found to be the result of ethnic stratification (Patkar, et al., 2001).
