of findings from genetic studies, model organisms and molecular studies in humans has led to the hypothesis of a biological underpinning to heroin dependence, with particular emphasis on the role of the central nervous system [3]. This has inevitably led to an interest in genes encoding molecules in neural systems; these represent biologically plausible candidate genes and those involved in reward-processing, cognition, stress and anxiety have been studied most intensively [4]. As opioid receptors are critical for modulating the euphoric effects of the drug, variants in the genes encoding the opioid receptors have been tested extensively and there is good evidence in support of the A118G polymorphism in the mu opioid receptor gene (OPRM1) [5,6], albeit with mixed results. A recent meta-analysis has conducted a thorough analysis of this polymorphism, by defining uniform phenotypes across a range of addictive substances, including heroin, and reported a modest protective effect of the G allele in European populations [7]. Other neural systems have also been tested, including the dopaminergic, glutamatergic, GABAergic, and serotonergic [8–10] systems. The candidate gene approach relies on a prior hypothesis of functionally plausible genes, yet has yielded few robust or replicated findings, being limited by a number of flaws
