Investigations of candidate genes other than those coding for alcohol metabolizing enzymes in Native American populations have thus far included those genes involved in drug-reward pathways, serotonergic genes, and positional candidates based on previous linkage studies. For example, polymorphisms in the CNR1 gene, which encodes for the cannabinoid receptor type 1, have been related to a number of alcohol, cannabis, and other substance use phenotypes in multiple populations including the COGA sample [52]. In the California Indian sample, CNR1 polymorphisms were associated with a trait measure of impulsivity [53]. Trait impulsivity is hypothesized to underlie the lack of behavioral control associated with substance use disorders, and thus, this finding suggests that CNR1 may act as a general risk factor for alcohol and drug misuse.
