Expression quantitative trait loci
An expression quantitative trait locus is a type of trait locus">Phenotypic trait">trait locus, a genomic locus that is associated with phenotypic variation for a specific, quantifiable trait. While the term QTL can refer to a wide range of phenotypic traits, the more specific eQTL refers to traits measured by gene expression, such as mRNA levels. Although named "expression QTLs", not all measures of gene expression can be used for eQTLs. For example, traits quantified by protein levels are instead referred to as protein QTLs.
Distant and local, trans- and cis-eQTLs, respectively
An expression quantitative trait is an amount of an mRNA transcript or a protein. These are usually the product of a single gene with a specific chromosomal location. This distinguishes expression quantitative traits from most complex traits, which are not the product of the expression of a single gene. Chromosomal loci that explain variance in expression traits are called eQTLs. eQTLs located near the gene-of-origin are referred to as local eQTLs or cis-eQTLs. By contrast, those located distant from their gene of origin, often on different chromosomes, are referred to as distant eQTLs or trans-eQTLs. The first genome-wide study of gene expression was carried out in yeast and published in 2002. The initial wave of eQTL studies employed microarrays to measure genome-wide gene expression; more recent studies have employed massively parallel RNA sequencing. Many expression QTL studies were performed in plants and animals, including humans, non-human primates and mice.Some cis eQTLs are detected in many tissue types but the majority of trans eQTLs are tissue-dependent. eQTLs may act in cis or trans to a gene. The abundance of a gene transcript is directly modified by polymorphism in regulatory elements. Consequently, transcript abundance might be considered as a quantitative trait that can be mapped with considerable power. These have been named expression QTLs. The combination of whole-genome genetic association studies and the measurement of global gene expression allows the systematic identification of eQTLs. By assaying gene
expression and genetic variation simultaneously on a genome-wide basis in a large number of individuals, statistical genetic methods can be used to map the genetic factors that underpin individual differences in quantitative levels of expression of many thousands of
transcripts. Studies have shown that single nucleotide polymorphisms reproducibly associated with complex disorders as well as certain pharmacologic phenotypes are found to be significantly enriched for eQTLs, relative to frequency-matched control SNPs. The integration of eQTLs with GWAS has led to development of the transcriptome-wide association study methodology.