A second set of factors specifically hypothesized to improve the power to identify genetic variants related to substance use disorders are collectively referred to as endophenotypes. Electrophysiological measures provide one example of an endophenotype for substance use disorders. Electrophysiological measures are highly heritable indices of brain function shown to be relevant to the processes involved in the development of substance dependence both in the general population [32], as well as in Native Americans [33]. Evidence that EEG measures represent specifically promising endophenotypes for substance use disorders has been presented in a number of studies published using the COGA dataset [see 34]. Similar findings in Native American populations have now been described in several studies [35-39]. In one study of the California Indian population [38], EEG alpha phenotypes were found to be heritable (0.67), and in a second study [37] linkage analysis revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1p36.31-p36.22 and 6p21.1. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4q22.1, 11p14.1, 14q32.2, 16q12.2 for
