Addiction study to examine interaction of genes and environment

One of several to focus on common conditions, personal environmental exposures

A psychiatric geneticist at Washington School of Medicine in St. Louis is one of several principal investigators around the country who will participate in the Genes, Environment and Health Initiative (GEI), a unique collaboration between geneticists and environmental scientists. The $48 million initiative is sponsored by the National Institutes of Health (NIH).

Laura Jean Bierut, M.D., professor of psychiatry at the School of Medicine, will head the national study of addiction, looking both at genetic and environmental factors that contribute to the problem. The co-principal investigator also is a Washington University faculty member, John Rice, Ph.D., professor of mathematics in psychiatry and of biostatistics.

“Addiction is a classic condition requiring the interaction of genetic, environmental and behavioral factors,” Bierut says. “A person with a genetic tendency to become addicted to alcohol, nicotine or other drugs will never develop that addiction if that individual never drinks, smokes or uses. We want to get a better handle on how genes and environment interact to cause disease.”

Bierut and the other investigators involved in GEI projects will conduct whole genome association studies of problems from addiction and diabetes to heart disease and tooth decay. Whole genome association studies can identify specific points of variation in human DNA that underlie particular conditions. Identifying genetic factors that influence health, disease and response to treatment is believed to be central to discovering and developing next-generation medicines that target diseases with increased precision and reduced risk.

Virtually all diseases have a hereditary component, transmitted from parent to child through the 3 billion pairs of DNA letters that make up the human genome. When researchers completed the final analysis of the Human Genome Project in April 2003, they confirmed that the 3 billion base pairs of genetic letters in humans were 99.9 percent identical in every person. But housed within that remaining 0.1 percent is the mystery of why some people are more or less susceptible to particular conditions than their neighbors or even other members of their own families. That miniscule variation explains why some people inherit relatively rare disorders, such as cystic fibrosis and muscular dystrophy, or inherit an increased risk for more common problems such as cancer, heart disease, diabetes and addiction.

“This is ground-breaking research in understanding the complex factors that contribute to health and disease,” says U.S. Department of Health and Human Services Secretary Mike Leavitt. “Researchers have long known that our genes, our environmental exposures and our own behavioral choices all have an influence on our health. This new initiative will use innovative genomic tools as well as new instruments for measuring environmental factors — from diet and physical activity to stress and substance addiction — in order to begin sorting out how these different factors affect a person’s risk for a number of health conditions.”

To identify genetic risks, researchers will rely on the newfound ability to swiftly identify genetic differences throughout the genome between people with an illness and those who are healthy, leading to a better understanding of the underlying genetic contribution to the disease. The environmental component of the projects will begin by developing new technologies that accurately measure personal exposures with small, wearable sensors that can be used to assess environmental agents. The final component of the research strategy is to determine whether the effect of genetic variants that increase disease risk is different in the presence of environmental exposures. In the first year of the initiative, the NIH will fund eight genome-wide association studies, two genotyping centers, a coordinating center and more than 30 environmental technology projects.

“Genome-wide association studies have proven themselves to be powerful tools for discovering the genetic contributions to common diseases,” says Elias A. Zerhouni, M.D., director of NIH, which is part of the Department of Health and Human Services. “Early findings from such studies have identified new genetic variants contributing to a higher risk of common diseases such as prostate cancer, diabetes and heart disease, but researchers have only scratched the surface. The genetic studies being funded today will identify many novel genetic variants contributing to an increased risk for these health conditions.”

The genome-wide association studies will be led by the National Human Genome Research Institute (NHGRI), part of NIH. First-year funding for the studies was contributed by all NIH institutes and centers, including an extra investment of approximately $3.4 million by NIH’s National Institute of Dental and Craniofacial Research (NIDCR).

For the first year of the project, the principal investigators, approximate funding levels and health condition to be focused on are:

Terri Beaty, Ph.D., Johns Hopkins University, Baltimore, $622,000,

International Consortium to Identify Genes and Interactions Controlling Oral Clefts.

Laura Bierut, M.D., Washington University School of Medicine, St. Louis,

$561,000, Study of Addiction: Genetics and Environment.

Eric Boerwinkle, Ph.D., The University of Texas Health Science Center, Houston, $257,000, Genome-wide Association for Gene-environment Interaction Effects Influencing Coronary Heart Disease.

Neil Caporaso, M.D., National Cancer Institute, Bethesda, Md., $349,000,

A Genome-wide Association in a Population-based Lung Cancer Study.

Frank Hu, M.D., Ph.D., Harvard University, Cambridge, Mass., $622,000, Genes and Environment Initiatives in Type 2 Diabetes.

William Lowe, M.D., Northwestern University, Chicago, $572,000, Genome-wide Association Mapping: Maternal Metabolism-Birth Weight Interactions.

Mary Marazita, Ph.D., University of Pittsburgh, Pittsburgh, $492,000, Dental Caries (Tooth Decay): Whole Genome Association and Gene x Environment Studies.

Jeffrey Murray, M.D., University of Iowa, Iowa City, Iowa, $488,000, Genome-wide Association Studies of Prematurity and Its Complications.

“In the past, hunting for the genes causing any disease has been a long and arduous task, but the biomedical tools and technologies now available to researchers are breathtaking,” says Francis S. Collins, M.D., Ph.D., NHGRI director and co-chair of the NIH coordinating committee for GEI. “These tools will enhance how we predict, diagnose and ultimately design personalized prevention and treatments for our patients.”

Bierut says that’s a particularly important issue in the study of addiction.

“We know from past research that these behaviors tend to cluster in families,” she says. “Large studies of twins previously concluded that the clustering is partly related to genetic factors. But environmental and behavioral factors also play a role. We hope the GEI project helps us to clarify how all of those factors interact.”

Background information on genome-wide association studies can be found at Background information on environmental impacts on health can be found at

NIEHS, a component of the National Institutes of Health, supports research to understand the effects of the environment on human health. For more information on environmental health topics, visit

NHGRI is one of 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Extramural Research supports grants for research and for training and career development at sites nationwide. Additional information about NHGRI can be found at its website,

The National Institute of Dental and Craniofacial Research is the Nation’s leading funder of research on oral, dental and craniofacial health. Additional information about NIDCR can be found at its website,

The National Institutes of Health (NIH), the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.