Factors associated with heterogeneity in microarray gene expression in peripheral blood mononuclear cells from large pedigrees
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BACKGROUND: Genome-wide microarray expression is a rich source of functional genomic data. We examined evidence for differences in expression from peripheral blood mononuclear cells between individuals, examined some of factors that may be responsible and provide recommendations for analysis. METHODS: A total of 643 individuals from 17 large Mexican American pedigrees had microarray gene expression data generated from peripheral blood mononuclear cells. This data has previously been used to map cis- and trans-expression quantitative trait loci using genome-wide linkage analysis. We estimated both principal components and cell proportions in these data, and tested them for association with clinical factors to provide insight into causes of variation in gene expression between individuals. RESULTS: We identified that there were highly significant differences in the second principal component of gene expression between pedigrees, with 3 pedigrees being outliers. The estimated cell proportions identified 1 individual who was a gross outlier, as well as pedigrees that differed from others in their estimated proportions of helper and cytotoxic T cells. CONCLUSIONS: These phenomena could be from either pedigree-specific genetic variation, technical artefacts, or clinical factors. Incorporating factors that influence gene expression into genetic analysis, and exclusion of outliers could improve the power of genetic mapping of expression traits.