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 The ADH1C gene belongs to the biologically relevant alcohol-metabolising alcohol dehydrogenase (ADH) genes. The p-value of this SNP, which was at position 282 of our top-down ranking, achieved a p=2.84×10-4 in the GWAS. It would not have been carried forward into the follow-up study if it had not been supported by evidence from our animal study. In order to achieve a power of 80% to detect significant association withstanding correction for multiple testing, we would have needed to include 5573 patients and 8900 controls (regarding actual OR and MAF of this SNP). The same is true for our replicated association to marker rs11640875 which had rank no. 510 in our GWAS findings. It is located in the cadherin 13 (CDH13) gene, a gene which has been described in previous studies as a susceptibility locus for both alcohol dependence25 and methamphetamine dependence.73 Increasing sample sizes is often not feasible and bears the risk of increasing clinical as well as genetic heterogeneity.
