Genetics and circadian rhythms: Connecting your DNA to your body’s internal timekeeper

Circadian rhythm is an important factor in one’s health during space travel, where maintaining a stable sleep schedule can be difficult. Disruptions in circadian rhythm don’t just affect quality of sleep but also overall health, and genetics play an important role. Researchers at Baylor College of Medicine’s Translational Research Institute for Space Health (TRISH) explored the human genetic variations that determine 24-hour rhythmic gene expression and disease risk.

“Some people wake up earlier, and some people wake up later. How does genetic variation affect that?” said Dr. Dongyin Guan, assistant professor of molecular and cellular biology at Baylor and TRISH investigator. “What is the circadian rhythm in a peripheral tissue, like the muscle, liver or heart? There’s no such study. This is a knowledge gap.”

Guan and Dr. Ying Chen, postdoctoral associate in endocrinology at Baylor and TRISH co-investigator, along with their research colleagues, sought to address that gap.

Think of your genes as a light switch that can turn off and on at certain times throughout the day to keep your body running smoothly. The team found that people’s genes follow different daily rhythms depending on their unique genetic makeup. They systematically identified and mapped rhythmic quantitative trait loci (rhyQTLs), special spots in your DNA that influence how your genes turn on and off over a 24-hour period, like an internal clock.

The team grouped people based on their genetic differences and explored how these differences are associated with daily rhythms in 45 organs. However, there was more daily rhythm in gene expression than expected – Chen and Guan discovered 4 times more circadian genes than previously known, more than they had even imagined.

“These additional new identified rhythmic genes are more related to theological functions like muscle performance and heart rate,” Guan said.
Dr. Rihana Bokhari, scientific research director at TRISH and assistant professor in the Center for Space Medicine at Baylor explains the importance of this research for astronauts.

“During space travel, astronauts’ circadian rhythms are very disrupted. They don’t see a sunrise and sunset on a scale that’s normal to us. They circle the Earth and see the sunrise and sunset almost every 90 minutes, so they don’t have that biological drive from the circadian side,” she said Dr. Rihana Bokhari. “We are working on early stages of trying to understand how that disruption might affect disease risk biology.”

Space health research to understand the genetic factors that could impact an individual’s sleep rhythm also can be beneficial to those on Earth who may not have typical sleep schedules, like shift workers, who undergo frequent circadian disruptions.

As this research progresses, it could one day be integrated into personalized health plans, recognizing that each person’s circadian rhythm is unique. People metabolize medications differently, have various sleep patterns and even digest food more efficiently at different times of the day. Since this field is still in its early stages, there is much more to uncover and understand.

“Our next goal is to examine the process at a more functional level of proteins and metabolites, and how genetic variation contributes to these disruptions,” Chen said. “Think of the body like a factory and our genes are the instructions, and gene expression tells us which instructions are being read. To really understand what is happening, we need to look at what the ‘workers’ – which are the proteins – are doing and what ‘products,’ the metabolites, are being made.”

This study opens a door to understanding how our unique genetic makeup shapes the daily rhythms that keep our bodies in balance. By looking at rhyQTLs, this research shows that gene activity is not the same for everyone. The findings of this study have important implications not only for the average person, but also for astronauts, whose body clocks are often disrupted in space due to not seeing the sun the same as us here on Earth.

Understanding the genetic factors that play a part in one’s circadian rhythm can help tailor health strategies for space missions, where maintaining as much circadian balance as possible is key to success. This research not only deepens our understanding of human biology but also lays the groundwork for optimizing health in extreme environments like space.

By Keri Ogle, communications fellow at the Translational Research Institute for Space Health