Previous studies were somewhat inconsistent regarding associations with alcoholism and related traits. The discrepancies may be due to a number of reasons. Most obviously, these include type II error and low power due to sample size limitations for some studies. Second, most subjects were diagnosed according to the ICD(World Health Organization) or DSM(American Psychiatric Association) system. However, ICD-10 criteria for AD have been shown to be more stringent than DSM-IV criteria, which in turn are more stringent than DSM-III-R(Schuckit et al. 1994). Therefore, different studies differ in their diagnostic criteria, and selection of more severely affected subjects could potentially increase the observed effect sizes. Third, different recruiting strategies could result in differing results (e.g., recruitment based on clinical treatment samples vs. that based on general population samples). Fourth, studies using only males or females may yield different results than studies using mixed sex samples, especially when this affects sex matching between cases or controls. Fifth, the genetic effects of ADH1C 350Ile may change over the course of lifetime alcohol use. For example, it may be a protective factor at one
