Unlocking the Relationship Between Genetics and Disease

Princeton University researchers map genetic variants and gene expression levels on different chromosomes.

 Genes determine cell functioning and other biologic activities. They, therefore, clearly play a role in disease development. Fifteen years after mapping of the human genome, however, much remains to be understood about just how genes are involved in the emergence and behavior of different diseases. New research by a team of scientists at Princeton University may fill in some of those knowledge gaps.

The team analyzed 7,000 tissue samples from 449 deceased donors to map transexpression quantitative trait loci (trans-eQTLs), the links between genetic variants and gene expression levels on different chromosomes. Trans-eQTLs are important because they may provide key information about how specific genes are lined to specific traits, but they are difficult to map. So far the group has published results obtained for 44 different human tissue types.

The initial efforts have revealed information about genes involved in thyroid cancer. A specific genetic mutation known to increase the risk of thyroid cancer is located next to the protein FOXE1, a transcription factor 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.

The Princeton group is part of the National Institutes of Health-funded Genotype-Tissue Expression (GTEx) Consortium comprising researchers from 80 academic institutions investigating gene expression and regulation with the intention of better understanding how interactions between genes, and between genes and the environment, contribute to diseases. The GTEx Consortium is working to collect additional tissue samples so scientists can gain a deeper understanding of trans-eQTLs and how they affect the evolution of many complex diseases. 

Other groups are focused on the link between genes and cancer development and progression. Researchers at the University of Michigan recently reported links between gene mutations and the likelihood of the spread of certain solid tumors based on the analysis of gene-sequencing data from 500 cancer patients. Separately, scientists at the University of Maryland used a statistical-analysis method to identify mutations that drive 20 different cancer types.


Nigel Walker

Mr. Walker is the founder and managing director of That’s Nice LLC, a research-driven marketing agency with 20 years dedicated to life sciences. Nigel harnesses the strategic capabilities of Nice Insight, the research arm of That’s Nice, to help companies communicate science-based visions to grow their businesses. Mr. Walker earned a bachelor’s degree in graphic design with honors from London College.