In conclusion, these data represent the first linkage analysis of a level of response to alcohol phenotype in American Indians. The results suggest that several areas of the genome may harbor genes that modulate an individual’s level of response to alcohol. Loci highlighted in prior studies in this population as well as other populations for substance dependence phenotypes were identified including a site on chromosome 10 previously identified for this FIRST FIVE SRE phenotype in the COGA study. The results of this study should, however, be interpreted in the context of several limitations. Level of response to alcohol was evaluated using the SRE, and a more direct measure of intoxication using and alcohol challenge protocol combined with objective and subjective measures of intoxication may produce more reliable results. Additionally, the findings may not generalize to other Native Americans or represent all Indians of the tribes studied, and comparisons of linkage findings to non-Indian populations may be limited by differences in a host of potential genetic and environmental variables. Despite these limitations, this report represents an important step in an ongoing
