Expression level of many mRNA genes shows abundant natural variation in human populations. The quantitative variations in mRNA expression are thought to contribute to phenotypic differences between individuals. Several molecular mechanisms have been identified that control gene expression. In addition to known transcription factors that bind to specific regulatory DNA sequences 
and extensively studied genetic polymorphisms that determine transcription level via cis
- or trans
, newly discovered miRNAs have been proven to be a major player in posttranscriptional regulation of gene expression 
. The miRNAs were first identified to play a role in developmental timing of Caenorhabditis elegans
in the early 1990s 
. Subsequent studies have shown that cellular factors necessary for miRNA biogenesis and many miRNAs are conserved in many organisms, suggesting the importance of miRNAs during developmental processes and evolutions 
miRNAs are a novel class of non-coding small RNAs which have been recognized as global regulators of gene expression that control the key cellular processes such as growth, development and apoptosis 
. A single miRNA can potentially regulate several hundreds of mRNAs forming a complex regulatory network that can act in a flexible manner for precise and rapid effects on protein translation and gene expression. Majority of the miRNAs are expressed in a cell- or tissue-specific manner and may contribute to the establishment and/or maintenance of cellular and/or tissue identity. It is estimated that several thousand human genes, up to about one-third of the mRNA transcriptome, are potential targets for regulation by miRNAs encoded in the genome 
. The regulatory process occurs posttranscriptionally and involves miRNA interaction with a target site in the mRNA that has partial or complete complementarity to the miRNA. The regulatory effect of miRNAs on gene expression is a complex process involving both translational repression and accelerated mRNA turnover, each of which appears to occur by multiple mechanisms. Moreover, certain miRNAs are also capable of activating translation 
. Hence, miRNAs are related to diverse cellular processes and regarded as important components of the gene regulatory network.
Importance of an individual miRNA is reflected in the diseases that may arise upon the loss, mutation or dysfunction of specific miRNAs 
. One study reported mutations in 5 of 42 sequenced miRNAs in 11 of 75 patients with chronic lymphocytic leukemia. Although the majority of these mutations were somatic, at least one was germline 
. Another study showed that up-regulation of several miRNA genes was correlated with loss of their target gene transcript (KIT) in papillary thyroid carcinoma. In 5 of 10 such cases, this down expression was associated with germline single-nucleotide changes in the two recognition sequences in KIT for these miRNAs 
. Recently, a series of papers presented conceptually related ideas linking the genetic variations and alterations of biogenesis and function of miRNAs to the increased risk of developing sixteen major human diseases. Significant role of miRNAs in the pathogenesis of many major human disorders has been proposed as part of disease phenocode concept 
. These results suggest that germline changes in miRNAs and their target genes may have a profound effect not only on disease progression but also an individual's risk of developing disease.
Current studies, however, have focused primarily on miRNA role as posttranscriptional regulators of target mRNAs or at a much higher level on their cell biological processes and organismal roles 
. Loss- or gain-of-function studies often analyzed effects on mRNAs by expressing or suppressing specific miRNA in cells. As these experiments create non-physiological levels of miRNAs that may affect target mRNAs abnormally, accurate evaluation of the miRNA effects may require normal range of variations in miRNA expression under an endogenous condition. Additionally, because miRNAs can interact with their target genes directly and influence expressions of many other genes indirectly, the miRNAs may demonstrate correlations with their target genes as well as non-target genes. Therefore, merely measuring target gene expression may not be sufficient to gain understanding miRNA regulatory effects. A complimentary approach is to identify downstream genes that are tightly correlated with fluctuation of miRNA expression. Liu et al 
has reported significant miRNA correlations with target genes as well as non-target genes by performing expression profiling analysis on 12 brain tumor biopsies. Subsequent experimental validations demonstrated a directional causal relationship from miRNAs to mRNAs. However, the small sample size and potential mutations in the samples restrained statistical power to detect weak correlations.
To fully examine the miRNA-mRNA correlations at whole genome scale, we measured both miRNA and mRNA transcriptional profiles in 90 human Epstein-Bar virus transformed lymphoblastoid cell lines. We performed pair-wise correlation coefficient analysis and identified strong correlations between the endogenous variations in the miRNA and mRNA expression. Gene Ontology (GO) analysis identified over-representation of these miRNA-correlated genes in several biological processes. These high-throughput expression data provides a valuable resource to examine global effects of miRNAs on gene expression and hence on complex traits.