E. Failure to document evidence for substance dependence genes of major effect in most populations There are few careful studies of the ways in which most human addiction vulnerabilities move through families (eg segregation analyses). No such study indicates a “major” gene effect on addiction vulnerability in most current populations. There is an exception: the “flushing syndrome” variants at the aldehyde (ALDH) and alcohol (ADH) dehydrogenase loci in Asian individuals do provide genes of major effect in this population. Individuals with these gene variants are at lower risk for becoming dependent on alcohol than individuals with other genotypes [57] in Chinese [58, 59], Korean [60], Japanese [61–66] and other populations [67, 68]. Homozygous ALDH2*2 individuals are strongly protected from alcohol dependence [61, 62]. This locus thus provides a good example of “primary” pharmacogenomics, though in a restricted population.
