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. Experience from GWAS into diabetes, for example, has shown that differences in assessment can jeopardize even the most robust findings.74 Obtaining very large sample sizes may necessitate inclusion of samples from different cultural and ethnic backgrounds which can also increase heterogeneity. The ADH1C gene belongs to the ADHclass I genes (ADH1A, ADH1B and ADH1C) which have been extensively investigated for the risk of alcohol dependence, initially in Asian75,76,77and subsequently in African78,79and European80-84populations. A metaanalysis85 reported a significantly higher risk of alcohol dependence among carriers of the ADH1C*2 allele (OR=1.91) in East Asian populations, but its role in the European population is less clear. Our associated marker rs1614972 is in complete LD (D'=1.0; r2=0.311, HapMap) with one of the two polymorphisms of the ADH1C*2 protein isoform that has recently been investigated in 575 patients and 530 controls from the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample. The two marker haplotype comprised of markers rs1614972 and rs1693482 yielded evidence
