Identifying cis- and trans-acting single-nucleotide polymorphisms controlling lymphocyte gene expression in humans

Abstract Assuming multiple loci play a role in regulating the expression level of a single phenotype, we propose a new approach to identify cis- and trans-acting loci that regulate gene expression. Using the Problem 1 data set made available for Genetic Analysis Workshop 15 (GAW15), we identified many expression phenotypes that have significant evidence of association and linkage to one or more chromosomal regions. In particular, six of ten phenotypes that we found to be regulated by cis- and trans-acting loci were also mapped by a previous analysis of these data in which a total of 27 phenotypes were identified with expression levels regulated by cis-acting determinants. However, in general, the p-values associated with these regulators identified in our study were larger than in their studies, since we had also identified other factors regulating expression. In fact, we found that most of the gene expression phenotypes are influenced by at least one trans-acting locus. Our study also shows that much of the observable heritability in the phenotypes could be explained by simple single-nucleotide polymorphism associations; residual heritability was reduced and the remaining heritability may represent complex regulation systems with interactions or noise