Association of a functional mu-opioid receptor allele (+118A) with alcoholdependency

Genetic association studies have implicated the TaqI A1 allele of the human dopamine D2 receptor gene (DRD2) as a risk-determining factor for alcohol dependency. However, as alcoholism is a disease of polygenic inheritance, t he percentage of overall disease variance explained by the TaqI A1 allele i s small. In searching for other genetic loci that may, either alone or in c ombination with DRD2, enhance prediction of alcoholism, we have found a nov el association between a functional coding variant (+118A) within the human mu-opioid receptor gene and alcohol dependency. However, no association wa s detected between the DRD2 TaqI A1 allele and alcoholism in our sample nor did we find synergy between +118A and TaqI A1 alleles on prediction of ris k for the disease. These results suggest that, at the molecular level, the endogenous mu-opioid receptor system is a contributing factor to the etiolo gy of alcoholism. (C) 1999 Wiley-Liss, Inc.