Several studies have shown that the μ-opioid receptor is involved in the reinforcing effects of drugs. The most extensively studied variation in OPRM1 is Asn40Asp (rs1799171), but the findings are not consistent [31,32]. Asn40Asp is an A/G transition at the 118th nucleotide of the coding sequence, causing an amino acid change at position 40 from asparagine (Asn) to aspartate (Asp). This change leads to the loss of a putative N-glycosylation site in the extracellular region. The Asp40 allele is associated with higher β-endorphin affinity, lower blood cortisol levels and higher aggressive threat scores as compared to the Asn40 allele. A recent meta-analysis including 28 distinct samples and over 8000 subjects concludes that this polymorphism does not increase the risk of substance dependence [33]. In our study, this polymorphism itself is not significant. However, we do notice that this polymorphism is in high LD with the core markers defining the associations with both SI and ND. Marker combination 1-3-5-6-7 produces very similar p values as that observed with the core markers (see Table 4, comparing combinations 1-3-5-6-7 and 5-6-7). These results
