Rapid Publication A Genome Screen of Maximum Number of Drinks as an Alcoholism Phenotype

The Collaborative Study on the Genetics ofAlcoholism (COGA) is a multicenter re-search program to detect and map suscepti-bility genes for alcohol dependence and re-lated phenotypes. The measure M of“maximum number of drinks consumed in a24-hour period” is closely related to alcohol-ism diagnosis in this dataset and provides aquantitative measure to grade nonalcoholicindividuals. Twin studies have shownlog(M) to have a heritability of approxi-mately 50%. Genome screens for this traitwere performed in two distinct genotypedsamples (wave 1 and wave 2), and in thecombined sample. MAPMAKER/SIBS wasused to carry out Haseman-Elston based re-gression analyses. On chromosome 4, an un-weighted all-pairs multipoint LOD of 2.2was obtained between D4S2407 andD4S1628 in wave 1; in wave 2, the regionflanked by D4S2404 and D4S2407 gave aLOD of 1.5. In the combined sample, themaximal LOD was 3.5 very close to D4S2407.This evidence for linkage is in the region ofthe alcohol dehydrogenase gene cluster onchromosome 4. These findings on chromo-some 4 are consistent with a prior reportfrom COGA in which strictly defined nonal-coholic subjects in wave 1 were analyzed.The present analysis on log(M) allows moreindividuals to be included and thus is poten-tially more powerful. Am. J. Med. Genet.(Neuropsychiatr. Genet.) 96:632–637, 2000.