Bivariate genome scans incorporating factor and principal component analyses to identify common genetic components of alcoholism event-related potential and electroencephalogram phenotypes

摘要

Genetic components significantly contribute to the susceptibilities of alcoholism and its endophenotypes, such as event-related potential measures and electroencephalogram. An endophenotype is a correlated trait which identifies individuals at risk. Correlated traits could be influenced by shared genes. This study is intended to identify chromosome regions that may harbor common genetic loci contributing to alcoholism, event related potential measures and electroencephalogram. All 143 Collaborative Study on the Genetics of Alcoholism families with 1,614 individuals provided by the Genetic Analysis Workshop 14 were used for the analysis with aldx1 as an alcoholism diagnosis. We carried out factor and principal component analyses on the 12 event-related potentials, then bivariate genome scans on aldx1 and electroencephalogram (ecb21), as well as alcoholism and the principal component scores of the event-related potential measures. A univariate genome scan was also carried out on each trait. Factor and principal component analysis on the event-related potential measures showed that the 4 ttths and 4 ntths belong to one cluster (cluster 1), while the 4 ttdts belonged to another (cluster 2). From each cluster, one principal component was extracted and saved as pc1 (for cluster 1) and pc2 (for cluster 2). The results of genome scans revealed only one chromosome region, chromosome 4 q at about 100 cM, identified by several univariate genome scans including aldx1, ecb21, and pc2, and the evidence of linkage increased significantly in the bivariate genome scans of aldx1 and ecb21 and aldx1 and pc2. Our study suggests that the same quantitative trait locus on the chromosome 4 q region, where ADH3 is located, may influence the risk of alcoholism, variations of electroencephalogram, and the 4 ttdts of the event-related potential measures.