Biological sex affects genes for body fat, cancer, birth weight

September 10, 2020

CHICAGO --- Biological sex has a small but ubiquitous influence on gene expression in almost every type of human tissue, reports a new study from Northwestern Medicine, the University of Chicago and the Centre for Genomic Regulation in Barcelona. Gene expression is the amount of product created by a gene for cell function.

These sex differences are observed for genes involved in many functions, including how people respond to medication, how women control blood sugar levels in pregnancy, how the immune system functions, and how cancer develops.

The study will be published September 10 in Science.

Sex also has a weaker but important effect on how genetic variation between individuals impacts their gene expression levels. The scientists discovered 369 instances where a given genetic variant present in males and females impacted gene expression to a different degree in each sex. This enabled the scientists to discover 58 previously unreported links between genes and complex traits such as blood pressure, cholesterol levels, breast cancer and body fat percentage.

"These discoveries suggest the importance of considering sex as a biological variable in human genetics and genomics studies," said project leader Barbara Stranger, an associate professor of pharmacology at Northwestern University Feinberg School of Medicine.

By taking an approach that specifically looks for differences between males and females, the scientists discovered previously unknown links between specific genes and specific human traits that were missed by approaches that considered males and females as a single group. Furthermore, the study reported a portion of previously reported gene-trait links were true only for a single sex.

"The significance of this is if specific genes or genetic variants contribute differentially to a given trait in males and females, it could suggest sex-specific biomarkers, therapeutics and drug dosing," Stranger said. "In the future, such knowledge may form a critical component of personalized medicine or may reveal disease biology that remains obscured when considering males and females as a single group."

Sex differences exist for many human traits and disease characteristics (e.g., age of onset, severity, response to treatment) and have been previously attributed to hormones, sex chromosomes and differences in behavior and environmental exposures. But the molecular mechanisms and underlying biology remain largely unknown.

In this study, scientists investigated sex differences in the human transcriptome, which is the sum of all RNA transcripts in a cell, from 44 types of healthy human tissue from 838 individuals. For each gene, the scientists tested whether the average amount of gene expression in females differed from the amount in males.

They discovered more than a third of all human genes (37%) were expressed at different levels in males and females in at least one type of tissue. Although these effects were abundant, the amount that gene expression differed was mostly small.

The genes with differential expression between males and females represented diverse molecular and biological functions, including genes relevant to disease and clinical traits, many of which had not been previously associated with sex differences.

All of these gene-trait associations suggest a causal link between specific genetic variants and a trait.

"Finding these links helps us to understand the biology underlying the trait," Stranger said. "If we understand the biology of a trait, we can try to use that information for diagnostics, drug development and predicting outcome."

In women, the genetic regulation of CCDC88 expression is strongly associated with the progression of breast cancer. The finding could motivate researchers to assess whether gene expression of CCDC88 is a useful biomarker for cancer progression in women, Stranger noted.

HKCD1 was associated with birth weight in women. Researchers hypothesize that HKDC1 may impact birth weight through altering glucose metabolism in the liver of a pregnant woman.

In men, DPYSL4 was associated with body fat percentage and CLDN7 with birth weight.

The genetic regulation of C9orf66 in males was associated with balding patterns in males. Prior to this study, little was known about the gene. With this discovery, investigators can design experiments to better characterize the role of this gene in balding patterns in males.

The study has some limitations. The researchers note despite extensive sex differences at the transcriptome level, the majority of human biology at all levels is shared between males and females. The findings are based on a snapshot of mostly older individuals. The analysis also does not account for sex differences that occur during different developmental stages or in specific environments.
-end-
The research is supported by the National Institutes of Health.

Northwestern University

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
Brightsurf.com 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 Amazon.com.