Newswise — African-Americans don’t get kidney stones as frequently as Caucasians. Are they protected genetically? If so, identifying the genetic factors that retard kidney stone formation could lead to new ways to treat or even prevent this painful condition, according to Vanderbilt University researcher Todd Edwards, Ph.D. Kidney stones afflict one of every 11 Americans and cost the country more than $2 billion annually. Avoiding them “could really make a difference for a lot of people,” and could cut health costs dramatically, he said.
Until recently, teasing out complicated kidney stone genetics would have required years of study, tens of thousands of patients and hundreds of millions of dollars. Now thanks to BioVU, Vanderbilt’s massive DNA databank, the mother lode is within reach. This month BioVU logged in its 150,000th unique genetic sample. It is now the world’s largest collection of human DNA linked to searchable, electronic health information, said Dan Roden, M.D., assistant vice chancellor for Personalized Medicine at Vanderbilt and BioVU’s principal investigator. BioVU began collecting DNA in 2007. Discarded blood specimens from Vanderbilt patients are sent to the DNA Resources Core, where the genetic material is extracted and stored. If patients check a box on a consent form, their leftover blood will not be used, but few choose to “opt out.” The DNA samples are bar-coded and, along with their matching electronic health records, scrubbed of information that could identify individual patients. The resulting genetic “gold mine” enables Vanderbilt researchers to quickly pull and analyze the DNA of hundreds of people with particular health conditions or responses to medication. Before proceeding, BioVU investigators must be approved by Vanderbilt’s Institutional Review Board, sign a data use agreement, and determine, with the help of a BioVU project manager, the feasibility of their idea. Their proposals are then considered by separate pre-review and full review committees consisting of Vanderbilt faculty members. To date, more than 50 BioVU studies have been approved and are under way. Researchers are seeking the genetic underpinnings of abnormal heart rhythms, Alzheimer’s disease, bipolar disorder, breast cancer, Crohn’s disease, diabetes, heart attack, high blood pressure, multiple sclerosis, prostate cancer and rheumatoid arthritis. The research is “groundbreaking,” said BioVU program manager Erica Bowton, Ph.D. “We’re actually changing clinical care from what we’re learning … That’s why I like this job.” For example, Stephen Bruehl, Ph.D., professor of Anesthesiology, is studying genetic factors involved in pain and pain management. In particular, he and his colleagues are studying whether a specific genetic variation affects patients’ response to pain medications following surgery. From the BioVU storehouse, they pulled the DNA samples of approximately 850 patients who received pain medication after undergoing total knee replacement at Vanderbilt and whose “pain ratings” were noted by nurses in their electronic health records. “We’re almost to the point where we can start piecing all of this together,” Bruehl said at a recent BioVU symposium. If patients with the genetic variation experience more pain, routine genetic testing prior to surgery could identify those who need a higher dose or different medication. Edwards, an assistant professor of Medicine, is investigating the genetic risks for kidney stones in African-Americans with collaborators from University of North Carolina at Chapel Hill and the University of Washington. This study is unique because people of recent African ancestry are protected from kidney stones compared to Europeans, cases are rare, and the causes for the difference in risks are unknown. Discovering genetic factors associated with kidney stones in a protected population may provide novel insights into the biology and evolution of stone formation. It could lead to a genetic test to identify high-risk patients and to prophylactic measures — including lifestyle changes — to help them avoid the condition. Edwards and his colleagues also are searching BioVU for genetic factors that may explain why African-Americans are less likely to suffer bone fractures from osteoporosis and, with his wife, Digna Velez Edwards, Ph.D., why they are more likely to develop uterine fibroids. For Edwards, who received his Ph.D. in Human Genetics at Vanderbilt in 2008 and joined the faculty two years later, BioVU represents a tectonic shift in health care that is uniting the fields of genetics, informatics and epidemiology, the study of diseases across populations. It’s a two-way street, he added. Discoveries made thanks to BioVU certainly will influence patient care. Likewise, changes in clinical care, including the digitizing of patient information, will change research, for example, by raising new questions. “With these new tools, like BioVU, we can really begin to create these bridges between communities of very sophisticated people,” Edwards said. “These conversations are really just beginning.”
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