A big step forward in linking the genome to disease risk

Discovering links between genetic variants and gene expression levels on different chromosomes could unlock the mysteries behind several diseases.

The human genome was first mapped about 15 years ago, but scientists have yet to gain a complete understanding of how genes maintain health—and how they govern the emergence of certain diseases. Now, a team of researchers led by Princeton University has taken a big step towards reaching that goal, publishing data related to 44 different human tissue types that they believe will help unlock the relationships between genetics and hard-to-treat diseases.

The team took 7,000 tissue samples from 449 deceased donors and used them to map transexpression quantitative trait loci, or “trans-eQTLs,” which are links between genetic variants and gene expression levels on different chromosomes. It’s those trans-eQTLs that are particularly difficult to map, but that may ultimately provide the most useful clues for linking genes with complex traits, many scientists believe. Their results were published in the journal Nature.

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The Princeton team is part of the Genotype-Tissue Expression (GTEx) Consortium, a group of researchers from 80 academic institutions who are funded by the National Institutes of Health and are pursuing projects designed to elucidate gene expression and regulation. Their goals are to better understand how interactions between genes, and between genes and the environment, contribute to diseases ranging from cancer to autism.

The Princeton research is ongoing, but this latest study did yield key revelations about genes and thyroid cancer, according to a release. The scientists discovered that a particular genetic mutation that’s known to raise the risk of the disease is located next to a protein called FOXE1, which is a “transcription factor”—a protein that regulates the activity of genes in the thyroid.

"Many thyroid diseases will be impacted by changing the expression levels of the thyroid-specific transcription factor, so we want to investigate FOXE1 more carefully in future work," said study co-author Barbara Engelhardt, assistant professor of computer science at Princeton, in the release.

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That work will build on a wider effort in the scientific community to determine how genes affect the development and progression of cancer. In August, scientists at the University of Michigan published gene-sequencing data from 500 cancer patients that uncovered links between certain mutations and the likelihood of solid tumors to spread. Earlier this year, a team of scientists at the University of Maryland described how they used a statistical-analysis method they developed to identify mutations that drive 20 different cancer types.

The GTEx Consortium aims to collect more tissue samples so scientists can gain a deeper understanding of trans-eQTLs and how they affect the evolution of many complex diseases.