In conclusion, these data represent the first association analysis of a level of response to alcohol phenotype with multiple SNPs in the OPMR1 receptor gene in American Indians. SNPs highlighted in prior studies of substance dependence phenotypes were also identified as well as new SNPs of potential importance to substance dependence research. The results of this study should, however, be interpreted in the context of several limitations. A more conservative approach to multiple comparisons would have led to fewer significant effects. Level of response to alcohol was evaluated using the SHAS-E, and a more direct measure of intoxication using the SHAS or body sway may produce more reliable results. Haplotype analysis using the SNPs typed in this study was unable to specially tag all of the clades observed in the HapMap population. Ultimately, a more complete analysis depends on resequencing the OPRM1 and determining which sequence variants have functional significance. Additionally, the findings may not generalize to other Native Americans or represent all Indians of the tribes studied, and comparisons of association findings to non-Indian populations may be limited by
