Not all rare coding variants in the MOR were genotyped in this study. We focused our efforts on coding variants with a frequency of 0.5–5% located in the main OPRM1 isoform (MOR-1). The minor allele frequency cut-off was set at 5% to find variants with a strong effect on phenotype; these are typically kept at a low frequency in the population due to purifying selection. The lower threshold for our SNP selection criteria was set at 0.5% to provide sufficient power to detect associations. By focusing on these variants we did not assess the contribution of ‘personal’ SNPs to the risk for addiction. There are 34 ‘personal’ SNPs recorded in the NHLBI-ESP database for the OPRM1 gene. It is likely that a subset of these variants increase the risk for addiction; however, it is not possible to test the effects of these variants using the classical case-control association approach. Furthermore, coding variants in the less well characterized isoforms of OPRM1 may also be relevant for drug addiction risk and these variants could be of interest for future studies.
