Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials

The availability of robust quantitative biological markers that are correla ted with qualitative psychiatric phenotypes can potentially improve the pow er of linkage methods to detect quantitative-trait loci influencing psychia tric disorders. We apply a variance-component method for joint multipoint l inkage analysis of multivariate discrete and continuous traits to the exten ded pedigree data from the Collaborative Study on the Genetics of Alcoholis m, in a bivariate analysis of qualitative alcoholism phenotypes and quantit ative event-related potentials. Joint consideration of the DSM-IV diagnosis of alcoholism and the amplitude of the P300 component of the Ct event-rela ted potential significantly increases the evidence for linkage of these tra its to a chromosome 4 region near the class I alcohol dehydrogenase locus A DH3. A likelihood-ratio test for complete pleiotropy is significant, sugges ting that the same quantitative-trait locus influences both risk of alcohol ism and the amplitude of the P300 component.