There are several other genes that have been shown to contribute to the risk of alcohol dependence as well as key endophenotypes. The earliest genes were typically identified as a result of family-based analyses. In most cases, studies recruited families having multiple members with alcohol dependence; such families are likely to segregate variants that affect the risk of alcohol dependence. The most common initial approach was linkage analysis, in which markers throughout the genome were measured to identify chromosomal regions that appeared to segregate with disease across many families. Linkage studies are relatively robust to population differences in allele frequencies (because they test within-family inheritance), and can find a signal even if different variants in the same gene or region are responsible for the risk in different families. The drawback to this approach is that linkage studies find broad regions of the genome, often containing many hundreds of genes. In many cases, the initial linkage studies were followed by more detailed genetic analyses employing single nucleotide polymorphisms (SNPs) that were genotyped at high density across the linked regions. Some of
