For decades, scientists have carefully elucidated the role of genes in disease by examining how subtle differences in a person’s genetic information affect their lifetime risk of developing common diseases such as cancer, diabetes, and heart disease.
But genetics are only part of the story.
The rest comes from all the external and internal exposures a person experiences during their lifetime, from pollution to infections to diet and lifestyle. Cumulatively, these exposures and the body’s biological response to them make up what scientists call an exposome.
A team led by scientists at Harvard Medical School has now conducted what is believed to be the largest study ever to quantify the relationship between exposure and health outcomes, testing more than 100,000 associations. This study shows the importance of studying potential environmental disease risks collectively, rather than one at a time.
Analyzing existing survey data from the U.S. population, researchers found that individual exposure had only a moderate effect on health outcomes, but the effect increased when multiple exposures were taken into account at the same time.
Although a single exposure may not result in a significant change in health, the cumulative soup of exposures can be as powerful as your DNA in determining your risk for a particular disease. ”
Chirag Patel, first author, Associate Professor of Biomedical Informatics, HMS Blavatnik Institute
The findings were published on March 18th. natural medicinedemonstrate the value of using existing data for exposomics research and highlight the need for larger studies to identify what combinations of exposures have the greatest impact on human health and disease.
It is hoped that a deeper understanding of the human exposome will provide insights that researchers, clinicians, and patients can use to improve health at the individual level.
I will borrow the blueprint.
Patel and senior author Arjun (Raj) Manrai, assistant professor of biomedical informatics at HMS, trace their foray into exposome research back to their interest in precision medicine, a field dedicated to developing disease treatments tailored to individual patients.
“Historically, this field has been unbalanced. A lot has been done on the side of using genetics to personalize treatments, but not much has been done on the environmental exposure side,” Patel said.
Manray pointed out that many studies look at single exposures and health effects, but this one-at-a-time approach often produces contradictory results. For example, whether a random ingredient in a cookbook is harmful, beneficial, or unimportant to human health.
Patel and Manrai recognized the need for comprehensive research that systematically and simultaneously examines the relationships between many environmental exposures and health effects.
“We wanted to build a robust, large-scale overview of these associations for the exposome,” Manray said.
To do so, Manray and Patel collaborated with John Ioannidis, a physician-scientist at Stanford University who specializes in meta-research and large-scale analyses.
The research team borrowed the blueprint from genetics research. This research is known for its comprehensive research, including genome-wide association studies (GWAS), which scan entire genetic information to examine associations with diseases.
In fact, Patel and Manrai are part of the U.S. Exposomics Network and the Human Exposome Project, which was conceived in the vein of the Human Genome Project.
Exploring the exposome
In the new study, researchers analyzed 20 years of existing data from the Centers for Disease Control and Prevention’s annual National Health and Nutrition Examination Survey (NHANES).
They tested more than 115,000 associations between 619 environmental exposures and 305 clinically relevant health outcomes. Exposures include things like pollutants and nutrients, while health effects include things like BMI, blood sugar levels, and lung function.
The team identified more than 5,600 associations that were considered statistically significant.
A single exposure explained less than 1% of the variation in health outcomes between people in hundreds of health outcomes. Considering up to 20 exposures at a time, this explanatory power increased to an average of 3.5% of the 120 health outcomes. This is comparable to the contribution of several individual genetic variations.
The results revealed some particularly strong associations between exposures and outcomes. For example, a combination of 20 specific exposures, including trans fats, common pollutants called polychlorinated biphenyls, and vitamin E levels, explain 43 percent of the variation in people’s triglyceride levels, which are risk factors for heart disease.
The researchers emphasized that, despite their extensive explanatory power, most combinations of exposures can only explain a small amount of variation between people.
“Overall, there is no conclusive evidence. Every exposure seems to be slightly important, but when you consider them together, the exposures become even more important,” Patel said.
starting point
The study provides a “snapshot of exposure” that will serve as a starting point for future exposome studies, the researchers said.
Patel and Manrai hope to further expand the scope of environmental exposure and health effects, investigating the link between early exposure and later disease.
They are also interested in whether and how information about exposure should be incorporated into the tools clinicians use to assess a patient’s risk of developing diseases such as heart disease, and the tools patients use to understand their health status.
To help other research groups further explore the associations uncovered in this study, the research team made their data and software freely available online to other research groups in The Phenome-Exposure Atlas of Health and Disaster Risk.
“Such large-scale analyzes are an agnostic, systematic method for generating hypotheses, but determining causality requires detailed mechanistic assessments of exposure-disease associations,” Manray said. “We’re zooming out to see where we can zoom back in.”
The potential to apply exposomic insights to protect health is particularly meaningful in an era when many people wear devices that continuously monitor a wide range of health indicators, the authors said.
“It may seem like a Star Trek-esque vision, but I see a future where exposomic information is integrated into these systems using AI, allowing people to understand in real time how their exposure impacts their health on a day-to-day, even hour-by-hour basis,” Patel said.
sauce:
Reference magazines:
Patel, C.J.; Others. (2026). An atlas of the relevance of exposomes and phenomes in health and disease risk. natural medicine. DOI: 10.1038/s41591-026-04266-0. https://www.nature.com/articles/s41591-026-04266-0
