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GTEx project sheds light on gene expression

Scientists from the Genotype-Tissue Expression (GTEx) project have completed a range of studies documenting how small changes in the DNA sequence can impact gene expression across tissue types.


The GTEx project, a National Institutes of Health-funded consortium including researchers from the Broad Institute of MIT and Harvard, launched in 2010. The aim was to build a catalogue of genetic effects on gene expression across a variety of human tissues. Consequently, this would provide insight into the molecular mechanisms of genetic associations within complex diseases and traits. This would also help develop our understanding of regulatory genetic variation. The project set out to collect biospecimens from ~50 tissues from up to ~1000 post-mortem donors. Additionally, the project aimed to create standards and protocols for optimising post-mortem tissue collection and donor recruitment, biospecimen processing and data sharing.

A 10-year effort

Ten years on since its initial launch, the GTEx Consortium released their final set of studies last week. The 15 new papers are based on the GTEx version 8 dataset. This dataset is a deep survey of tens of thousands of regulatory variants. The group published five of the papers in Science and another five in Genome Biology. They also published two in Science Advances, one in Cell, one in Genome Medicine and one in Genetic Epidemiology.

Their flagship paper, published in Science, detailed the results from the consortium’s 10-year effort to reveal the complexity of gene expression. The team presented analyses performed on 15,201 samples from 49 tissues of 838 post-mortem donors. Each donor underwent whole-genome sequencing to detect genetic variants. In addition, RNA sequencing was also performed for all tissues to establish gene expression patterns across tissues. Key methodologies used by researchers were expression quantitative trait locus (eQTL) analysis and splicing QTL (sQTL) analysis. This helped in identifying variants affecting gene expression. The data confirmed that eQTL effects are typically either tissue-specific or shared across most tissues. The team also revealed differences in QTL effects between sexes and across different populations. Overall, they showed that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

Work still to be done

These studies constitute the most comprehensive catalogue of genetic variations that affect gene expression to date. The collection comprises of the consortium’s final analyses of the GTEx dataset. However, the team emphasise that our understanding of genetic effects on cellular phenotypes is yet to be complete. They suggest that further investigation into genetic regulatory effects in specific cell types, study of additional tissues and developmental time points, incorporation of diverse molecular phenotypes and continued investment in the diversity of sample populations will help to transform scientific discoveries.

Kristin Ardlie, co-corresponding author on the flagship paper, stated:

“GTEx was an ambitious, complex undertaking, and it remains very difficult to access this breadth of tissues from individuals, and in that sense GTEx was unique and has helped pave the way for studies like the Human Cell Atlas.

But we really need large-scale resources like this and others, such as ENCODE, from which we can glean complementary information to get a more complete picture of the molecular mechanisms that drive biology.”

Image credit: Background photo created by kjpargeter –

More on these topics

Consortium / Gene Expression / Variants