Skip to content

GTEx Bulk RNA-seq

The Genotype Tissue Expression (GTEx) project1 generates useful datasets via the analysis of diverse tissues from post-mortem human donors.

One important class of GTEx dataset records levels of RNA expression across a wide range of tissues. These GTEx RNAseq datasets can help us discover the tissues in which a particular gene plays an important role. For instance, if we find that across many donors, the RNA transcripts of a gene are over-expressed in the colon relative to other tissues, it is reasonable to assume that the gene plays its most important role in the colon.

GTEx bulk tissue RNA-seq datasets are used by the gene set analysis step of MAGMA to construct hypotheses about which tissues are most involved in a trait or disease. Continuing the above example, MAGMA works on the principle that if most of the genes strongly associated with a disease are over-expressed in the colon according to GTEx RNAseq data, it is likely that the colon is central to the disease process.

Artifacts in GTEx RNAseq data

Finucane et al.2 applied Gene Ontology Enrichment Analysis to the genes expressed in lung tissue in the GTEx bulk RNAseq dataset. They found strong enrichment for immune-related genes. They hypothesized that this enrichment of immune genes in the lung was not a real property of lung tissue, but was instead a consequence of the presence of blood in the lungs of the post-mortem donors from which GTEx samples were collected. Users of GTEx datasets need to be aware of the presence of this kind of data artifact.

References

FUMA Tutorial (Discusses use of GTEx data for post-GWAS analysis)

GTEx Bulk Tissue Expression Data

GTEx paper

Alberts, Bruce, et al. Molecular biology of the cell: seventh edition. WW Norton & Company, 2022. See Chapter 6.

  1. GTEx Consortium. The GTEx consortium atlas of genetic regulatory effects across human tissues. Science, 369(6509):1318–1330, 2020. URL: https://www.science.org/doi/full/10.1126/science.aaz1776. ↩

  2. Hilary K Finucane, Yakir A Reshef, Verneri Anttila, Kamil Slowikowski, Alexander Gusev, Andrea Byrnes, Steven Gazal, Po-Ru Loh, Caleb Lareau, Noam Shoresh, and others. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nature Genetics, 50(4):621–629, 2018. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC5896795/. ↩