A multiple threshold liability model suggests linkage of alcohol dependence to three loci in the COGA data set

Previous analyses of the Collaborative Study on the Genetics of Alcoholism (COGA) data set have yielded suggestive linkage to various diagnoses of alcohol dependence on regions of chromosomes 1, 2, and 7. Suggestive linkage has also been reported on chromosome 4 for related phenotypes, including "Maximum Number of Drinks in a 24 Hour Period" ("Max Drinks"), "Pure Unaffected" Status, and certain ERP phenotypes. We propose a multiple threshold liability model to use the hierarchical nature of alcohol dependence diagnoses in the COGA data set. A linkage analysis using this model yielded three chromosomal regions with lod equivalent scores greater than 1.5. The first, on chromosome 1, gave a lod score of 2.59 at the marker D1S532, a marker inside the previously reported linkage region. The second, on chromosome 4 (lod 1.73) near the alcohol dehydrogenase (ADH) gene cluster is at the marker where the "Max Drinks" signal was reported, as well as near the "Pure Unaffected" signal. The last was on chromosome 8 at the marker D8S1988 (lod equivalent 2.16). Although no linkage has been reported in this region, it is homologous to a region on rat chromosome 5 which has been shown to have linkage to an alcohol consumption trait. Results for nicotine will also be discussed.