and statistical ground than most other such associations [Bierut and others 2012], it was also important to demonstrate the relationship in a genome-wide context. GWAS (hypothesis-free investigations) can be powerful in investigation of the genetic architecture of complex traits, such as alcohol drinking behaviors. GWAS of AD and maximum number of alcoholic drinks confirmed the protective effects of ADH1B rs1229984 and rs2066702 with respect to alcohol drinking behaviors in European-Americans and African-Americans [Gelernter and others 2014; Xu and others 2015]. On the basis of these previous GWAS, ADH1B rs1229984 and rs2066702 appear to have relatively large effect sizes on AD symptom count and maximum daily number of alcoholic drinks in European-Americans and African-Americans respectively (Table 3). Although these effect sizes are substantially larger than the average for alleles discovered in GWAS of complex traits, they explain very little of the variance of the alcohol use behaviors. Indeed, it is widely recognized that the predisposition to complex traits, such as alcohol use disorder, is highly polygenic with hundreds to thousands of loci likely involved [Loh and others 2015].
