A further 4 SNPs are intergenic and further eight SNPs are located in genes. No ontological relatedness was detected between these genes. That is not surprising, given the assumed genetic heterogeneity of alcohol addiction. In the Supplemental Text, we discuss data from linkage findings, biochemistry and animal studies that have provided evidence that these loci may be involved in alcohol dependence. However, none of these markers achieved genome-wide significance in our study. This does not necessarily disqualify them. Alcohol dependence is a complex and heterogeneous disorder that is influenced by multiple genetic, biological, psychological, and sociocultural factors. Formal genetic and linkage studies do not indicate the existence of genes with major effects in the European population. Thus, genome-wide significant findings in moderately-sized samples will be rare, but the number of replicable associations may actually be much larger. One replicated association that did not withstand correction for multiple testing was obtained with the SNP rs1614972 in the ADH1C gene. The ADH gene cluster is located on chromosomal region 4q, which is among the most consistently replicated loci contributing to alcohol phenotypes.72
