The National Institutes of Health announced today that it will fund 22 grants on genome-wide studies of how epigenetic changes -- chemical modifications to genes that result from diet, aging, stress, or environmental exposures -- define and contribute to specific human diseases and biological processes.
The awards will build on the important work undertaken as part of the NIH Roadmap for Medical Research's Epigenomics Program. Approximately $62 million will be awarded over the next five years to study the epigenome in a number of diseases and conditions, including tumor development, hardening of the arteries, autism, glaucoma, asthma, aging, and abnormal growth and development.
"Epigenomics represents the next phase in our understanding of genetic regulation of health and disease," says NIH Director Francis Collins, M.D., Ph.D. "These awards will address the extent to which diet and environmental exposures produce long lasting effects through changes in DNA regulation." The initiative was launched through the NIH Director's Office and, as part of the Roadmap, is expected to profoundly alter the way we understand, diagnose, and treat disease.
"This is the largest effort to date to apply epigenetics on a genome-wide scale to specific diseases," said James F. Battey, M.D., Ph.D., director of the National Institute on Deafness and Other Communication Disorders, one of the lead NIH institutes for this Roadmap program.
The Roadmap Epigenomics Program was designed to characterize epigenetic modifications and to correlate the presence or absence of specific modifications with disease status. DNA methylation is a fundamental epigenetic modification that regulates gene expression and chromosome stability. This and other epigenetic modifications control gene activity by changing the three-dimensional structure of chromosomes. (See scientific illustration of epigenetic mechanisms at http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp.)
The awards announced today are funded by 11 NIH institutes and the NIH Office of the Director and are part of the NIH Roadmap for Medical Research's Epigenomics Program that began in 2007. The NIH contributors include the National Cancer Institute, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health, and the Office of Behavioral and Social Sciences Research and the Office of Strategic Coordination in the NIH Office of the Director.
"The new grantees being announced will join a larger collaborative research effort that is working together to understand epigenetics and how it affects human health and disease," said Nora D. Volkow, M.D., director of the National Institute on Drug Abuse.
This health and disease-focused component of the NIH Roadmap Epigenomics Program builds on the previous four interrelated initiatives, but is the first to tackle questions related to diseases. The other four initiatives include the establishment of four epigenome mapping centers, the funding of an epigenomics data analysis and coordination center. the development of innovative technology in epigenetics, and the discovery of novel epigenetic changes.
"These studies will help increase our understanding of how factors such as environmental exposures, alcohol, drug abuse and stress can modify the effect of epigenetics on diseases," said Linda S. Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences.
The following awards are being made by NIH:
- David A. Bennett, Rush University Medical Center, Chicago, Exploring the role of the Brain Epigenome: Cognitive Decline and Life Experiences.
- Paul D. Coleman, Sun Health Research Institute, Sun City, Ariz., DNA Methylation in Alzheimer's Disease and Normally Aged Brain.
- Jessica J. Connelly, University of Virginia, Charlottesville, Epigenomics of Atherosclerosis.
- Francine Hughes Einstein, Yeshiva University, New York City, Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine Growth.
- Margaret Daniele Fallin, Johns Hopkins University, Baltimore, Environment, the Perinatal Epigenome, and Risk for Autism and Related Disorders.
- Gary Hugh Gibbons, Morehouse School of Medicine, Atlanta, Vascular Epigenome Dynamics in African-American Hypertensives.
- Tim H.M. Huang, Ohio State University, Columbus, Ohio, Epigenomics of Bisphenol A Exposure and Disease Risk.
- Terumi Kohwi-Shigematsu, Lawrence Berkeley National Laboratory, Berkeley, Calif., Determinants for Genome-Wide Epigenomics in Metastatic Breast Cancer.
- Yongmei Liu, Wake Forest University Health Sciences, Winston-Salem, N.C., Epigenome-Wide Association Study of DNA Methylation and Atherosclerosis.
- Stephen J. Meltzer, Johns Hopkins University, Baltimore, The Temporal Epigenomic Program of Barrett's Neoplastic Progression.
- Shannath L. Merbs, Johns Hopkins University, Baltimore, Pangenomic Analysis of DNA Methylation Marks in Glaucoma and Macular Degeneration.
- Jonathan Mill, King's College, London, A Multi-faceted Approach to Epigenomic Profiling in Alzheimer's Disorder.
- Roel A. Ophoff, University of California, Los Angeles, Epigenetic and Disease: The Role of DNA Methylation in Schizophrenia Susceptibility.
- Art Petronis, Centre for Addiction and Mental Health, Toronto, DNA Methylome Analysis in Bipolar Disorder.
- Gerd P. Pfeifer, City of Hope, Beckman Research Institute, Duarte, Calif., Aging and the Unstable Epigenome.
- Evan D. Rosen, Beth Israel Deaconess Medical Center, Boston, Epigenomics of Human Insulin Resistance.
- David A. Schwartz, National Jewish Health, Denver, Asthma: An Epidemic Caused by Epigenetics.
- Kathleen E. Sullivan, Children's Hospital of Philadelphia, Pa., Epigenomics of Systemic Lupus Erythematosus (SLE).
- Katalin Susztak, Yeshiva University, New York City, Epigenetics Landscape of Chronic Kidney Disease.
- Benjamin Tycko, Richard Mayeux, Columbia University, New York City, Epigenomics of Alzheimer's Disease.
- Kyoko Yokomori, University of California, Irvine, Epigenomic Analysis of Facioscapulohumeral Muscular Dystrophy
- Richard A. Young, Whitehead Institute for Biomedical Research, Cambridge, Mass., Epigenomic Mapping in Human Tumor Cells.
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