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Linking Genes, Environmental Exposure, and Disease

Using the NIEHS Environmental Polymorphisms Registry

Large cohort studies usually begin with a group of individuals who were exposed to a common risk factor or who exhibit a particular set of health traits. Researchers then analyze the individuals’ DNA for gene differences, also known as polymorphisms, that may be linked to disease.

But if scientists want to initiate cohorts the other way around, starting with polymorphisms to look for associated traits or disease risks, they might consider using the Environmental Polymorphisms Registry (EPR) (, a project sponsored by the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, N.C. The EPR provides access to DNA from more than 17,000 individuals, who may be called back for more detailed studies. By looking at DNA variants in the genes first, investigators can validate previous results and do more stringent biological experiments.

When the EPR was launched in 2005, its goal was to help researchers understand how the interaction between genes and environmental exposures led to the development of disease. As the number of DNA deposits grew, EPR administrators were pleased to find that their repository offered several advantages, one of them being its strong representation of minorities.

“The EPR was set up to reflect the diverse populations of North Carolina,” said Stavros Garantziotis, principal investigator in the NIEHS Laboratory of Respiratory Biology and medical director for the NIEHS Clinical Research Unit. “Now 25 to 30 percent of the active EPR population is African-American and approximately six percent is of Hispanic origin.”


How to Access EPR Samples

EPR offers an easy application process and is available to intramural researchers as well as other scientists interested in using its data. Detailed instructions appear on the EPR Web site (, but, essentially, scientists must:

  • Complete a request form
  • Submit a brief project proposal
  • Sign a Material Transfer Agreement

All documents must be submitted to Garantziotis by e-mail at He coordinates the EPR steering committee review. If approved, investigators receive DNA for analysis. If researchers want to take the project one step further and conduct a study by contacting EPR volunteers, the steering committee needs to authorize the project a second time before scientists go through the usual process of working with their Institutional Review Board (IRB). This additional EPR approval protects volunteers by affirming that the study is beneficial and worthy of their time.


Researchers who receive samples from the NIEHS EPR may use several techniques—such as microarray technology, shown above—to determine the function and expression levels of new genes.

One researcher involved in an ongoing EPR study is John Cidlowski, head of the NIEHS Laboratory of Signal Transduction. He studies glucocorticoids, steroid hormones that suppress inflammation, and their receptors. Previous research suggests that single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene increase the risk of cardiovascular events and metabolic syndrome in Caucasian populations.

But “the incidence of glucocorticoid receptor SNPs has not been well determined in non-Caucasian populations,” Cidlowski said. “So our lab is comparing gene expression profiles of macrophages isolated from EPR participants, which are then exposed ex vivo to glucocorticoids.


Powerful Genetics Tool

The EPR will be even more useful after three upgrades: a detailed questionnaire, the ability to use geospatial information, and, in the future, linking EPR to electronic medical records.

The questionnaire contains more than 100 questions that cover 30 major health topics, such as lung and heart health, endocrine and reproductive issues, and occupational exposures.

Geospatial Information Systems technology connects the EPR population to home addresses, which yield a wealth of knowledge including general location, census data, socioeconomic stresses, pollution exposures, and water sources.

Linking EPR volunteers to electronic medical records will give scientists instant access to cross-sectional and longitudinal health information so that they can follow the development and progression of a disease. “We will be careful to ask for consent and have it vetted by the IRB,” Garantziotis said.

With these added features, the EPR enhances its utility and reinforces its research significance by testing for complex diseases and uncommon traits that exist in the population.

The BTRIS Information Center

A Support Team Stands Ready to Help You


The support team at the BTRIS Information Center in the NIH Library will help investigators use a searchable repository of clinical research data (left to right, Rhonda Sanford, Shweta Bhangdia, Teferra Alemayehu, Mark Schermerhorn, and Jim DeLeo).

The BTRIS Information Center (BIC) opened on April 19, 2012, in the NIH Library through a combined effort of the members of the NIH Clinical Center and the NIH Office of Research Services. BTRIS—the Biomedical Translational Research Information System—is a user-searchable repository of clinical research data from the Clinical Center and other NIH Institutes and Centers. BTRIS development began in 2008 in the NIH Clinical Center Laboratory of Informatics Development (LID), which is under the leadership of Jim Cimino.BTRIS is available to all investigators working in human studies at NIH. It provides access to data associated with research subjects. In addition, BTRIS provides all NIH researchers access to all BTRIS data in subject de-identified form. BTRIS contains a vast amount of data, including laboratory results, vital signs, radiologic reports (with links to radiographic images), medication administration data, and clinical documents. It provides users with advanced search, filtering, and aggregation methods to create data sets to support ongoing studies and to stimulate ideas for new research.

Multiple reports are available through BTRIS—reports that can easily be produced with a user-friendly series of prompts. BTRIS also provides some analytic support tools such as the Lifelines2 visualization tool from the University of Maryland (College Park). LID’s Computer Science Section led by Jim DeLeo is also available for consultations and support pertaining to more specialized data analyses, especially analyses that support the translational research and translational medicine objectives of the NIH Roadmap. As BTRIS continues to develop, data from new sources and new report features will be added monthly.

The BIC, which is located on the first floor of the NIH Library near the information desk, provides information and general support to those wanting to use BTRIS to view, analyze, and extract BTRIS data. A basic kiosk BTRIS tutorial and handouts will be available whenever the library is open. Personnel trained to use the BTRIS will staff the BIC Monday through Friday from 8:30 a.m. to 3:30 p.m. They will demonstrate BTRIS and provide consultation on data access and data processing. For more information, contact Jim Cimino ( or 301-443-9696) or Jim DeLeo ( or 301-496-3848).

Additional support is available by calling the BTRIS Hotline (301-827-8270) and by e-mailing Also, an NIH-wide BTRIS Interest Group has been established to bring together present and prospective BTRIS users so they can communicate, learn and share experiences related to using BTRIS, and develop a voice, vision, and communication channel to enhance BTRIS service. See adjacent column for details on this interest group.

For more information about BTRIS, visit