There has been a plethora of studies that have investigated the relationship between a diagnosis of drug and/or alcohol dependence and the A118G polymorphism. The results have been conflicting and inconsistent. In a recent meta-analysis of 28 different studies, including over 8000 subjects, the conclusion was that the OPRM1 A118G variant did not appear to affect risk for substance dependence. However, the authors further speculated that additional research would be needed to determine whether another polymorphism in the gene might influence receptor function and thus risk for substance dependence [37]. An additional feature of these studies, that may have weakened the results, is the use of a dichotomous phenotype, drug dependence, a diagnosis that is made based on both heritable and non-heritable factors [38]. Town and colleagues [39] suggested that genetic studies on the influence of mu opioid receptors polymorphisms be viewed within the broader context of alcoholism where the opioid receptor genes are taken to be partial, rather than complete, risk factors for the disorder. Thus, it may be that polymorphisms in OPRM1 encode for a variant that influences
