With the increasing availability of genetic markers localized across the genome, more systematic approaches to gene identification have gained favor. Such studies are hypothesis free in their design, scanning large portions of the genome to identify regions that are significantly associated with the phenotype of interest. Linkage mapping was an early technique used to systematically scan the genome, in which approximately 400 to 1000 highly polymorphic markers were genotyped to test for genomic regions showing increased allele sharing among affected family members. Many large-scale alcohol-dependence gene identification projects have used genetic linkage mapping; the largest of these is the Collaborative Study of the Genetics of Alcoholism (COGA). COGA is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. The strongest linkage regions with alcohol dependence to emerge from this project were on chromosomes 4 and 7. Follow-up association studies of candidate genes in the linkage regions have identified association with several genes in each region, including GABRA2,48 NFKB1,51 ADH4, ADH1A, ADH1B,49 CHRM2,52 and TAS2R16.53 Although these studies illustrate the potential of genome-wide
