Seeking genetic clues to schizophrenia, bipolar disorder
Major VA trial will analyze DNA, clinical information from up to 38,000 veterans
A new study funded by VA will probe the genetic basis of schizophrenia and bipolar disorder, which together affect some 170,000 patients in VA's health system.
The $33-million effort will involve up to 38,000 veterans at about 25 VA sites—one of the largest single studies of its kind to date worldwide. The study will include up to 9,000 people with schizophrenia, 9,000 with bipolar disorder, and another 20,000 without either disease, as controls.
"We've been hunting for genes of susceptibility for these two diseases, and you need a very large sample to establish genome-wide association," says Larry J. Siever, MD, of the Bronx VA and Mount Sinai School of Medicine, one of the study's chairs.
Siever says veterans' genetic results—as well as other information they provide to the study team—will be linked to their VA medical records. That way, researchers can tap into richly detailed medical histories—sometimes decades long—and reveal links between genes and health problems.
"The VA is unique among U.S. health-care systems in having a great electronic medical record and cohort of people who stay in the system," says Siever. He says information gained through the study may be useful in follow-up efforts, as well.
The study leaders say strict privacy safeguards will be in place. For example, databases will be password-protected and specimens will be bar-coded and "de-identified." This means they can be traced back to the individual veterans who supplied them, but only by researchers who go through a strict approval process.
Veterans who volunteer for the effort will provide a blood sample from which their DNA will be isolated. The researchers, including a lab team at Yale University, will scan the DNA for hundreds of thousands of genetic variants. Those found in veterans with mental illness but not in "healthy" veterans will become suspects in the hunt for genetic risk factors. To date, a number of candidate genes have been linked to the two diseases, but none has yet led to concrete steps to boost care.
The researchers also hope to find genes tied to thinking problems and trouble with everyday tasks. Both types of symptoms are common in schizophrenia and bipolar disorder. Study volunteers will take pencil-and-paper tests that measure cognitive skills such as attention or memory. They'll also be observed writing checks, making telephone calls, and doing other everyday activities.
According to Siever, the ability to do such tasks—which can vary widely in people with serious mental illness—is a key predictor of overall function. He calls it "the great limiting factor determining whether people with schizophrenia or bipolar disorder can gain employment and function in society."
VA's chief deputy chief research and development officer, Timothy J. O'Leary, MD, PhD, says he expects the new study to have a major impact on care for the two diseases. "This research will be critical in helping us better understand the genetic basis of schizophrenia and bipolar disorder, which have such a huge impact within VA's health care system and in the nation at large. The knowledge gained through the study will no doubt lead to improvements in prevention, diagnosis and treatment."
Co-directing the study with Siever are Philip Harvey, PhD, with the Atlanta VA and Emory University; John Concato, MD, with Yale and VA's New Haven-based Clinical Epidemiology Research Center; and J. Michael Gaziano, MD, of VA's Massachusetts Area Veterans Epidemiology Research and Information Center. The study is funded by VA's Cooperative Studies Program.