To investigate the molecular genetics of alcoholism and depression, the COGA investigators performed linkage analyses. This means that they compared the presence of certain variants (i.e., alleles) of the markers in people with the ALC, AAD, AorD, and DEP phenotypes to identify chromosomal regions that were more similar in people with a given phenotype than would be expected by chance. Such regions would be considered genetically “linked” to the phenotype—that is, they are located near a gene that influences the phenotype. Because many genes appear to contribute to the risk for developing alcoholism, the investigators employed statistical methods that do not rely on specific models of susceptibility for the phenotype. All these statistical methods are based on the sharing of gene sequences that are identical by descent (IBD). Such sequences are considered IBD if both members of a sibling pair have inherited the sequence from the same parent. (For further discussion of linkage analysis for complex disorders, see Nurnberger and Berrettini 1998.) The investigators conducted multipoint linkage analyses, in which multiple markers were evaluated simultaneously for evidence of allele (gene sequence) sharing using the computer program ASPEX (ftp://lahmed.stanford.edu/pub/aspex/index.html).
