GTEx studies reveal variation in gene expression among individuals and, to small degree, by sex

September 10, 2020

Seven new studies from Science and Science Advances present the third and final phase of the Genotype-Tissue Expression (GTEx) project, begun over a decade ago by scientists aiming to better understand the effects of genetic diversity in healthy individuals. The results, based on an increased number of tissues and individuals, reveal population-specific and sex-specific differences in gene expression that could help inform how gene variants impact aging and disease.

One question the GTEx project explored is how sex differences in gene expression - which are broadly shared across mammals - differ in males and females. In a study in this package by Meritxell Oliva et al., researchers report that more than one-third of genes show sex-biased expression in at least one tissue, and that the genes that show differences between sexes are enriched for multiple pathways, including in immune responses and cancer. The authors hypothesize that this may contribute to the underlying sex-specific dysregulation for some diseases. The work of Oliva and colleagues also shows how sex differences in gene expression vary based on cell type within a tissue, and across the genome and between individuals. In a Perspective, Melissa A. Wilson highlights the utility of their findings to the research community - a resource that could be used for future comparisons with diseased tissues, she says. She notes that future studies that include samples from males and females will need to account for the findings: "different sex ratios in cell type in cases versus controls may drive the gene expression signal more than the phenotype of interest." Four other GTEx studies in Science discuss the effects of gene regulation in human tissues (Francois Aguet et al.), identify functional rare genetic variation (Nicole Ferraro et al.), study predictors of telomere length (Kathryn Demanelis et al.), and report cell type-specific gene regulation (Sarah Kim-Hellmuth et al.). In a study in Science Advances using data from 360,000 UK Biobank individuals, Aine Duffy et al. investigated how tissue-specific differences could be used to inform drug side effects that often account for the failure of drug clinical trials. Their work highlights the need for tissue-specific drug delivery. In a second study in Science Advances, Milton Pividori et al. used a tool called PhenomeXcan to analyze 4,091 traits from 49 tissues, results they converted into a gene-based, searchable platform including 22,515 genes. By applying a method to help identify likely causal gene-trait associations, their analysis helps inform which complex genetic traits may be therapeutic targets, which has been difficult to do in past.

In her Perspective, Wilson highlights the valuable contribution of this body of work and of its transparently shared sample set, but she also identifies sampling biases that hinder investigation of interindividual variation. Just over two-thirds of the samples are from males, more than half of the samples come from people 50 years and older, and nearly 85% of samples collected came from white people of European descent. She concludes: "Given these limitations of the samples, it is even more surprising--and should be motivating to human geneticists--how much interindividual variation is observed in gene expression among the people included in the GTEx Consortium. This should be a call to projects to expand the representation of human variation in future studies."

American Association for the Advancement of Science

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to