Understanding Disease Susceptibility through Population Genomics

Abstract

Genetic epidemiology studies have established that the natural variation of gene expression profiles is heritable and has genetic bases. A number of proximal and remote DNA variations, known as expression quantitative trait loci (eQTLs), that are associated with the expression phenotypes have been identified, first in Epstein-Barr virus-transformed lymphoblastoid cell lines and later expanded to other cell and tissue types. Integration of the eQTL information and the network analysis of transcription modules may lead to a better understanding of gene expression regulation. As these network modules have relevance to biological or disease pathways, these findings may be useful in predicting disease susceptibility.

Keywords: cis-acting; co-expression network; disease susceptibility; expression quantitative trait loci; trans-acting.

Fig. 1

The concept of expression quantitative trait loci (eQTLs). If transcript abundance depends on the genotype of a genomic locus, such a region is called an eQTL. If an eQTL is found inside or near the boundary of the target gene, it is classified as cis-regulatory (A); otherwise, it is trans-regulatory (B). In the latter case, the expression level of a target gene is not regulated by its cis-eQTL but through a regulator, such as a transcription factor (TF), whose expression is regulated by its cis-element.

Fig. 2

Comparison of average expression levels of all genes between two ethnic groups. The expression profile datasets of the International HapMap populations (European [CEU] and African [YRI]) measured in lymphoblastoid cell lines were downloaded from Gene Expression Omnibus (GEO accession no. GSE6536). For each of the 19,723 genes, the log-transformed expression levels of both 60 YRI and 60 CEU individuals were averaged and plotted on the x- and y-axis, respectively.