Understanding how genes and life experiences interact to affect health

Some children who experience early-life adversity — like abuse, neglect, a car accident, or the loss of a parent — show complete resilience to the experience and carry no negative health consequences into their later life. Unfortunately, many children who experience adversity face a wide variety of health problems, including increased risk for many diseases.

New research from the laboratory group of Idan Shalev, associate professor of biobehavioral health, found that clusters of genes expressed differently for children affected by early-life adversity.  Gene expression is how information stored in DNA is used to create a functional product, like RNA or proteins, and the process can be important to a person’s health.

Results of this study, published recently in Brain, Behavior and Immunity, demonstrated that early-life adversity can lead to a person’s genes expressing differently in some cases, potentially making people more susceptible to disease.

The researchers collected data from 29 young adults, about half of whom had experienced adversity in their early life. Each participant’s blood was collected multiple times across two separate sessions. During one session, participants were asked to complete a psycho-social stress test of public speaking and mental tasks in front of an audience in order to induce moderate stress. Then, their RNA in blood was analyzed to detect whether certain groups of genes were activated when they were and when they were not experiencing stress.

Relative to their peers who had not experienced adversity, people who experienced early-life adversity demonstrated different gene expression related to multiple cellular functions, including RNA splicing/processing, mitochondrial activity, and inflammation. Initially, these gene groups were overexpressed in individuals with early life adversity, but midway through the session, their expression levels declined, while those in the non-adversity group increased, demonstrating a crossover effect. The experiences of stress during the experiments, however, were not associated with expression of gene clusters regardless of people’s early-life experiences.

“We identified novel differences in the expression of genes controlling immune cell division and development and RNA production for individuals who experienced early-life adversity,” said Laura Etzel, first author of the paper who earned her Ph.D. in biobehavioral health from Penn State in 2022. “These genes regulate key processes of how our immune system is maintained and responds to our environment.”

This research identified some of the genetic pathways through which early-life adversity might lead to higher disease risk for people as they age. Individuals who have experienced early-life adversity face an increased risk of developing heart disease or certain cancers later in life, according to Etzel, who currently works as a research scientist at Duke University. The researchers said that future research can identify how these gene expression differences are linked to adversity.

“Our research ultimately aims to empower individuals who experienced early adversity to collaborate with their healthcare professionals to reduce future disease risk,” Etzel said.

Shalev agreed.

“Our lab is focused on understanding the myriad factors that can contribute to poor health outcomes among individuals who experienced adversity in early life,” Shalev said. “This study replicated previous links and added novel biological pathways that could impact long-term health. Our goal is to pinpoint behavioral and molecular targets for public-health observation and clinical treatments for individuals who experienced early-life adversity.”

The National Institute on Aging and the National Institute of Nursing Research supported this research.

Read the research.

Originally published in June 2024