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The NIH Catalyst: A Publication About NIH Intramural Research

National Institutes of Health • Office of the Director | Volume 31 Issue 1 • January–February 2023

Harnessing Exposome Data to Predict Disease

NIEHS Researchers Identify Environmental Exposures Associated with Type 2 Diabetes

BY MARLA BROADFOOT, NIEHS

Efforts led by researchers at the National Institute of Environmental Health Sciences (NIEHS) have demonstrated how knowledge of the exposome (external link), or the totality of our environmental exposures, can be harnessed to transform research on human health and disease. Now, the publication of a high-impact, clinically relevant paper from a decades-long study (external link) of environmental exposures demonstrates that a framework known as precision environmental health is coming of age.

Creating the evidence base

The Personalized Environment and Genes Study (external link) (PEGS) has collected health, family history, environmental exposures, and lifestyle data on more than 20,000 North Carolinians since its inception 20 years ago. The PEGS research team has compiled genetics data on a subset of that cohort by sequencing the whole genomes of 4,700 participants.

In a study published in November in the journal Diabetes Care (external link), NIEHS researchers examined how this data can be tapped to predict a person’s risk of developing type 2 diabetes (T2D). Using statistical methods and machine learning, they identified 76 environmental exposures associated with the disease (Diabetes Care DOI:10.2337/dc22-0295, 2022).

“We were able to recapitulate known risk factors, as well as identify previously unknown associations with asbestos and coal dust exposure, which was really interesting,” said lead author Alison Motsinger-Reif, Chief of the NIEHS Biostatistics and Computational Biology Branch.

Alison Motsinger-Reif

CREDIT: STEVE MCCAW, NIEHS

Alison Motsinger-Reif, Chief of NIEHS’s Biostatistics and Computational Biology Branch, used statistical methods and machine learning to identify environmental exposures associated with type 2 diabetes.

The team combined 13 of these environmental exposures to create a predictive value known as a polyexposure score. They compared the predictive performance of this score with a polygenic risk score based on genomic variants associated with diabetes and an overall clinical score built using established risk factors such as body mass index and prediabetes.

To their surprise, the researchers found that the scores based on environmental exposures provided a much stronger indicator of T2D odds than those based on genetics.

“Our findings provide a good demonstration of precision environmental health in one disease,” said Motsinger-Reif. She noted that her team can now expand this approach to other diseases such as hypertension, stroke, and other cardiovascular diseases.

The study is expanding in other ways. It is moving beyond self-reported environmental exposures to more granular and reliable measures such as incorporating geospatial data, epigenetic data, and health records data from partner institution—the University of North Carolina and Duke University.

Rick Woychik

CREDIT: STEVE MCCAW, NIEHS

Rick Woychik, Director of NIEHS and of the National Toxicology Program.

“We are now better positioned to advance the scientific framework we call precision environmental health,” said Rick Woychik (external link), Director of NIEHS and of the National Toxicology Program.

Precision environmental health combines environmental exposure research with genetic and epigenetic analysis to gain a more complete picture of a person’s disease risk. Precision environmental health is also informed by exposomics, and both are key focus areas for NIEHS that will be featured in the institute’s next strategic plan.

Catalyzing the conversation

The NIEHS efforts regarding the advancement of exposomics has included promoting the concept through meetings, workshops, and webinars, as well as supporting its implementation through technology development, infrastructure support, and funding individual studies, said Yuxia Cui (external link), Health Scientist Administrator in the NIEHS Exposure, Response, and Technology Branch.

Yuxia Cui

CREDIT: NIEHS

Yuxia Cui, Health Scientist Administrator in NIEHS’s Exposure, Response, and Technology Branch, co-organized a workshop series and an in-person summit where experts from around the globe gathered to brainstorm how knowledge of the exposome (the totality of our environmental exposures) can be integrated throughout health and disease research.

A recent series of virtual workshops, co-organized by Cui, continued those long-lasting efforts. The series, titled “Accelerating Precision Environmental Health: Demonstrating the Value of the Exposome (external link),” included five interactive virtual workshops and a summit held from July through September, 2022. The series employed the innovative open (external link)-space technology, a meeting format that allowed each workshop to be open, self-directed, and completely collaborative. As a result, everyone in attendance had a chance to set the agenda, lead discussions, and help create a path forward for the field. More than 400 unique individuals from around the globe participated.

One of the key outcomes from the workshop series was to collect data to help formulate an operational model for how to conduct experiments in exposomics. There was a consensus to establish guidelines for best practices and enable coordination among various exposome efforts. According to Cui, more than 200 pages of meeting reports emerged from the discussions, which will be helpful in defining next steps for operationalizing exposomics. A lot of work remains to be done, however.

“Those notes contain many great ideas proposed and research gaps identified that can inform individual researchers and programs as well as exposome initiatives supported by NIH or other institutions,” she said.

Currently, Cui and others at NIEHS are developing an operational model that will help investigators understand how to collect exposomic data that can be shared across the biomedical research community.


Marla Broadfoot

Marla Broadfoot is a writer and editor at the NIEHS Office of Communications and Public Liaison. In a former life, she was a postdoctoral fellow in clinical molecular genetics at the National Human Genome Research Institute. When she’s not writing, she likes to do yoga, foster puppies, and travel with her family.

graphic

CREDIT: NIEHS

Exposomics and precision environmental health are crosscutting research areas that involve not only NIEHS but also other institutes across NIH.

This page was last updated on Monday, January 9, 2023

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