Building a World-Class Genetics Research Program

With new funding and a growing biorepository, the Research Program on Genes, Environment and Health (RPGEH) is developing into an important resource to study the genetic and environmental causes of common diseases, such as heart disease, cancer, diabetes, high blood pressure, Alzheimer's disease, asthma, and many others. The research program is already supporting new research projects.

In the spring of 2007, RPGEH researchers began a survey of Kaiser Permanente members in Northern California. This health survey, completed by nearly 400,000 members, was a critical benchmark in establishing the program, because it provided important information about the background, lifestyle, and health behaviors of members.

In 2008, RPGEH researchers began re-contacting the 400,000 survey volunteers to collect saliva samples to obtain DNA for genetic analyses. By reaching out to various groups of Kaiser Permanente members, including participants in other large cohort studies, the RPGEH hopes to build the largest and most diverse population-based biobank in the United States.

The RPGEH ultimately plans to collect samples of saliva or blood from 500,000 members. In March 2009, nearly 70,000 saliva samples had already been collected.

Funding

The RPGEH was initially funded by grants from the Wayne and Gladys Valley Foundation and the Ellison Medical Foundation. Kaiser Permanente's Community Benefit Program has also provided important financial support for the program during the first several years.

In December 2008, the RPGEH received an $8.5 million grant from the Robert Wood Johnson Foundation Pioneer Program to support development of the biorepository through the collection of genetic samples. The grant will also support the continued development of the program's infrastructure and readiness to function as a resource for research projects on many common diseases.

An Environmental Database Like No Other

Sarah Rowell, MPH; Catherine Schaefer, PhD; Stephen K. Van Den Eeden, PhD and Lisa A. Croen, PhDRPGEH's infrastructure includes an environmental database that will hold a comprehensive array of data on the social and physical environment. "From the very beginning we have known that environment plays a very important role in common diseases. Genes are only part of the picture," says RPGEH Executive Director Catherine Schaefer, PhD.

Research carried out by the RPGEH will link environmental data to the neighborhoods where Kaiser Permanente members live. These maps of environmental data will allow researchers to measure the exposure of members to environmental factors and determine whether such exposures might be related to different health conditions.

To accomplish this, Senior Investigator Stephen K. Van Den Eeden, PhD, is heading an ambitious effort to collate data from various sources, including the RPGEH survey and California public databases. "When this is complete, we will have some of the most comprehensive environmental databases available," says Van Den Eeden. "Nobody else can bring these things fully together like Kaiser Permanente, partly because we are a very large integrated health system."

The environmental database will include data on air pollution, water quality, pesticide use, and Superfund sites. "We have an advantage in California because it has some of the richest databases," adds Van Den Eeden. Additionally, data is being gathered on Bay Area neighborhood characteristics, such as a community's proximity to parks, grocery stores, and healthy foods.

Other individual health-related data such as weight, prescription drug use, physical activity, and smoking habits will be collected as the project moves forward. The RPGEH is also collaborating with researchers at the University of California, San Francisco (UCSF) and the University of California, Berkeley, which have expertise in mapping environmental data and linking these data to better understand the environmental influences on health.

New Biorepository an Early Success

The RPGEH biorepository includes saliva samples from survey participants, and in the future will also include blood specimens. "Those specimens will allow us to do genetic research into the causes and outcomes of disease and will also allow us to look at things like drug reactions," says research scientist Lisa A. Croen, PhD, who heads up the biorepository effort. Eventually each participant's DNA sample will be combined with their individual health data and lifestyle information from the survey.

The nearly 70,000 saliva samples collected thus far already exceed numbers at established national biobanks. Schaefer notes that member information, whether it is from the survey, medical record, or DNA sample, is always obtained with the person's informed consent, and the privacy and security of data are carefully protected.

"We want to create a biorepository resource that is unique in terms of its size and composition and its ability to link large numbers of people with any type of disease or exposure," adds Croen. Over time, RPGEH researchers hope to collaborate with Kaiser Permanente's Regional Laboratory, which processes about 30,000 blood samples a day.

Prostate Cancer Research Focused on African-American Men

One of the first studies through the RPGEH is a genome-wide association (GWA)* study, led by Van Den Eeden and researchers from UCSF. The study, begun in early 2009 and funded by the National Cancer Institute, examines the genetic factors and risk of new prostate cancer in African-American men in Northern California.

The study is designed to look across the human genome to understand the genetic influences on this disease. The study includes 1,500 African-American men and 1,500 controls, all Kaiser Permanente Northern California members.

*A genome-wide association study is an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Courtesy: National Human Genome Research Institute.

Support and Guidance From Kaiser Permanente Leadership

A governance group that includes leadership from The Permanente Medical Group (TPMG) and Kaiser Foundation Health Plan at both the regional and national levels helps to guide the RPGEH and provide institutional support.

The RPGEH Scientific Advisory Panel includes worldwide experts. To ensure that the program continues to meet the needs of the community, the RPGEH meets quarterly with a 30-member Community Advisory Panel, led by Elize Brown, DrPH, JD, director of community research collaborations and acting administrative director at the DOR. The panel is representative of the racial, ethnic, and geographic diversity that comprises the Bay Area.

Bright Outlook

The next two years call for many exciting changes. Program leaders are currently planning to build permanent space for the program's biorepository, while also focusing on developing a more robust administrative structure. In 2008, Mary Henderson, MPH, MBA, joined the team as managing director. With 21 years of experience at Kaiser Permanente overseeing large-scale programs, Henderson will be responsible for directing nonscientific aspects of the program.

Mary Henderson, MPH, MBAIn addition to Henderson, Larry Walter has joined the program as the associate director for IT and informatics, and Sarah Rowell, MPH, is the new associate director of research operations.

Schaefer says that as the infrastructure is built, the RPGEH will seek to do research in a number of areas, including pharmacogenetic studies. "Kaiser Permanente is an excellent place to do pharmacogenetic studies because of our high-quality, long-term prescription and clinical data," she says. There is much work ahead to make such discoveries available to members and the community at large, says Schaefer, adding that the program will move beyond basic science and the discovery stage to perform research that looks at how to translate findings to the bedside.

"It is ambitious, but it separates us from some of the other biobank research programs focused primarily on the discovery phase of research."