Researchers at the Johns Hopkins University School of Medicine and four other academic medical centers have been awarded a $9.8 million grant from the National Institutes of Mental Health to pin down inherited changes that occur outside a cell’s DNA sequence in people with schizophrenia. Unlike changes or mutations in the DNA sequence itself, epigenetic marks or alterations can be affected by a lifetime of exposure to the environment in which cells operate.
“A comprehensive understanding of a disease’s epigenome can provide hidden and valuable clues to the role of diet, chemicals, infections and behaviors in genetic predisposition to diseases,” says Andrew Feinberg, M.D., professor of medicine and director of Hopkins’ Center for Epigenetics in its Institute of Basic Biomedical Sciences. Because a significant indicator of epigenetic change is our body chemistry’s addition of so-called methyl groups to DNA at specific sites, the research will focus on identifying changes in “methylated” sites in the epigenome that are associated with schizophrenia.
The research team is comprised of scientists at Hopkins, University of Pennsylvania, University of Alabama at Birmingham, University of Pittsburgh, and University of California San Diego. "The NIMH is very excited about funding this team of world-class scientists to look into epigenetic factors as possible causes for schizophrenia," says Thomas Lehner Ph.D., M.P.H., chief of the genomics research branch and the associate director of the division of neuroscience and basic behavioral science at the National Institute of Mental Health.
“Many researchers have identified genetic alterations associated with schizophrenia, but so far they do not account for a large proportion of schizophrenia patients,” says Feinberg, who is leading the multi-institutional effort. “Our work can identify differences in methylation patterns seen in blood samples or brain tissue samples from patients with and without schizophrenia to fill out the whole picture of both epigenetic and genetic contributions to this disabling disorder.”
The scientists will take advantage of DNA samples from the National Institutes of Mental Health genetics repository. They will analyze the methylation patterns at nearly ten thousand sites throughout the genomes of several thousand samples and controls, choose the 50 most prominent sites, and map the locations of the methylation marks to identify and analyze the activity of nearby genes.
“These studies will provide the first comprehensive evaluation of the epigenetics of schizophrenia and allow for unprecedented integration of genetic and environmental information about schizophrenia,” says Feinberg.
Because epigenetic changes — unlike nuclear DNA changes — are potentially reversible, “these studies may also lead to exciting new avenues for schizophrenia therapy,” Feinberg notes.
Stephen Desiderio, M.D., Ph.D., director of the Institute for Basic Biomedical Sciences at Hopkins, says the collaborative nature of the epigenome investigation “promises to add quickly and richly to the growing body of knowledge about schizophrenia,” which affects an estimated 2 million adults in the United States alone.
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