Other candidate genes that have shown evidence of association with alcohol and other drug misuse phenotypes in Native Americans includes OPRM1, which encodes for the mu opioid receptor and is the primary site of action for opioids such as morphine and heroin [59], the serotonin 1B receptor gene (HTR1B) [60], the catechol-O-methyltransferase gene (COMT), which encodes for an enzyme involved in synaptic dopamine metabolism, and the alpha-synuclein gene (SNCA), which encodes for a protein involved in dopamine neurotransmission. A summary of these and additional candidate gene studies of alcohol and other substance misuse phenotypes conducted in Native American samples is provided in Table 2. A review of this table highlights that with a few exceptions, these genes have been investigated in only a single study. Additionally, each of these genes have been studied in relation to alcohol and drug related phenotypes in other ethnic groups yielding a mix of both positive and negative results [21, 61]. Thus, given the low replication rate that has been noted for candidate gene studies of complex traits in general and for the relations between
