We also conducted a gene expression profiling study, using a sample size of 95 individuals, which resulted in the identification of only a small number of differentially expressed genes between individuals with low and high lymphocyte counts. We performed the gene expression study in Epstein-Barr virus (EBV)-transformed LCLs, which have been previously shown to be a useful model of gene regulatory phenotypes (12,17,19,40–44). It should be noted that both EBV transformation and cell line-specific artifacts can affect gene expression patterns (45–49). However, EBV transformation-driven expression patterns shared by all cell lines would not be classified as segregating with variation in lymphocyte counts. Furthermore, cell line-specific artifacts may increase the overall population variation in gene expression levels, but it is highly unlikely that these artifacts will stratify individuals based on their primary lymphocyte counts. Thus, the use of LCLs may result in reduced power to detect genes that are differentially expressed between individuals with high or low lymphocyte counts. However, genes with expression patterns associated with lymphocyte counts are more likely to be true positives than a private property of LCLs.
