One of the earliest genome-wide approaches to identifying genetic risk factors for alcoholism employed linkage mapping in large extended families or in many sibling pairs affected by alcohol dependence. Studies using this method identified several chromosomal regions with LOD (logarithm of the odds, to the base 10) scores suggesting that they contain loci influencing risk for alcohol dependence. The Collaborative Study on the Genetics of Alcoholism (COGA) investigators performed linkage studies on a large sample from the general US population using multigenerational pedigrees densely affected by alcoholism (45, 108). In contrast, investigators at the National Institute on Alcohol Abuse and Alcoholism conducted a linkage study on a more homogeneous population from a southwestern Native American tribe (88). Both of these studies provided evidence that loci on human chromosome 4 increase the risk for alcohol dependence. However, the linkage peak detected in the COGA study is near the alcohol dehydrogenase (ADH) gene cluster, whereas the linkage signal observed in the Native American sample is near the GABRB1 gene.
