Mapping complex disease traits with global gene expression

Abstract

Variation in gene expression is an important mechanism underlying susceptibility to complex disease. The simultaneous genome-wide assay of gene expression and genetic variation allows the mapping of the genetic factors that underpin individual differences in quantitative levels of expression (expression QTLs; eQTLs). The availability of systematically generated eQTL information could provide immediate insight into a biological basis for disease associations identified through genome-wide association (GWA) studies, and can help to identify networks of genes involved in disease pathogenesis. Although there are limitations to current eQTL maps, understanding of disease will be enhanced with novel technologies and international efforts that extend to a wide range of new samples and tissues.

Figure 1. eQTL mapping

Expression QTL mapping begins with the measurement of gene expression in a target cell or tissue from multiple individuals. This information is the substrate for investigating the effects of DNA polymorphism (of whatever type) on the expression of individual genes. Other factors which may alter transcription, such as epigenetic CpG methylation may also be mapped. Network analyses builds upon the strong correlations that are present between transcripts, and allows the identification of modules of genes that mediate complex functions. This information can then be made available to interpret genetic associations and mapping information from the study of complex disease.