"Genes and Environment" Grant Funds Close Look at Nature-Nurture Overlap in Common Diseases
Johns Hopkins’ McKusick-Nathans Institute of Genetic Medicine is one of two gene-hunting facilities in the nation to win a new $11.7 million four-year federal grant to rigorously sort out how such environmental factors as diet, exercise, stress and addictions interact with people’s individual genetic makeup to affect their risk for disorders as wide-ranging as cancer, diabetes, tooth decay and heart disease.
The Johns Hopkins Center for Inherited Disease Research (CIDR), a part of the McKusick-Nathans IGM, along with the Broad Institute of MIT and Harvard, will use advanced genotyping technology to identify specific genetic differences between those with and without particular medical conditions by searching their entire genomes. They will partner with eight teams of scientists from academic institutions around the country who have studied large numbers of people to identify gene and environment interactions in a variety of common disorders. Scientists at the University of Washington will co-ordinate the efforts of the consortium.
“Geneticists have known for some time that common diseases are the outcome of interactions between the genes we’re born with and how they respond to a lifetime of exposure to the environment around us,” says David Valle, M.D., director of the CIDR and Henry J. Knott Professor and director of the IGM. “But now that advances in technology and science have given us the tools to rapidly search whole genomes and to enumerate the millions of specific genetic differences between individuals, we can compare these differences between people who have a disease and those who do not. What is exciting about this project is that the investigators will also be keeping track of differences in environmental exposures. In this way, we will begin to learn how genetic variation, lifestyle, behavior and other environmental variables contribute to health and disease.”
CIDR, established in 1996, brings together scientists who specialize in genetics, genomics, molecular biology, statistics, medicine and bioinformatics to identify genes that contribute to so-called complex disorders, defined as common human diseases known to result from variations in many of our 22,000 genes as well as such external, environmental risk factors as smoking, air pollution, infections, drugs and nutrition.
In 2003, CIDR and the IGM’s Genetic Resources Core Facility teamed up to offer high-throughput genotyping as well as other services necessary for genome-wide association studies, including DNA isolation, amplification and quantitation, which will be offered as part of the GEI program.
Among other approaches, Hopkins’ CIDR specialists and the members of the GEI consortium will overlay individual variations in genomes with individual environmental histories to find patterns of associations and hunt down “connections” that occur most frequently in patients compared to a control population.
“Genome-wide association studies have proven themselves to be powerful tools for discovering the genetic contributions to common diseases,” said Elias A. Zerhouni, M.D., director of the National Institutes of Health. “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 specific projects for the GEI consortium are:
International Consortium to Identify Genes and Interactions Controlling Oral Clefts
Johns Hopkins University, Baltimore
Study of Addiction: Genetics and Environment
Washington University School of Medicine, St. Louis
Genome-wide Association for Gene-Environment Interaction Effects Influencing Coronary Heart Disease
The University of Texas Health Science Center at Houston
A Genome-wide Association in a Population-based Lung Cancer Study
National Cancer Institute, Bethesda, Md.
Genes and Environment Initiatives in Type 2 Diabetes
Harvard School of Public Health, Boston
Genome-wide Association Mapping: Maternal Metabolism-Birth Weight Interactions
Northwestern University, Chicago
Dental Caries (Tooth Decay): Whole Genome Association and Gene x Environment Studies
University of Pittsburgh, Pittsburgh
Genome-wide Association Studies of Prematurity and Its Complications
University of Iowa, Iowa City
The GEI genotyping centers:
Broad Institute of MIT and Harvard, Cambridge, Mass.
Center for Inherited Disease Research, Johns Hopkins University, Baltimore, Johns Hopkins University/Center for Inherited Disease Research
All studies will be coordinated by a center at the University of Washington, Seattle.