Replication of chromosome 4 candidate region for alcohol addiction through DNA pooling and individual genotype association studies with the marker D4S2407 in alcoholic and control japanese groups

A number of chromosomal locations potentially implicated in the etiology of alcohol addiction have been identified by linkage analysis (e.g. see Reich et al, 1998, Neuropsychiatrie Genetics 81: 207-215). We have investigated potential allelic association for markers within and flanking the cluster of alcohol dehydrogenase genes on chromosome 4 with alcoholism in the Japanese population. Allele image patterns (AIPs) for pooled samples (65 individuals from each group) have been generated and examined for significant differences - employing tech niques described previously (Hill et al, 1999, NeuroReport 10: 843-848) and any potentially significant results examined further by individual genotyping. Of the loci examined, allele patterns at both the D4S2361 and D4S2407 loci gave a delta AIP value of >0.25. On individual genotyping, no significant allele frequency differences between case and controls were observed for D4S2361 (p value for "clump" analysis = 0.8). In marked contrast, individual genotyping for D4S2407 indicated that the allele frequencies for the two groups were significantly different ("clump" analysis p = 0.01). Furthermore, a 2 x2 ² test for the nominated allele gave a p value = 0.002. These data provide strong motivation for a detailed investigation of the individual ADH genes which lie close to this marker.