Researchers to identify gene variants that cause ischemic stroke

Researchers from the University of Maryland School of Medicine are coordinating an international team of scientists working to identify genes or gene variants that may make a person more likely to have a particular type of stroke called an ischemic stroke. Ischemic strokes are caused by a blood clot in the brain and are the most common type of stroke, representing more than 80 percent of all cases. Stroke is a leading cause of disability and the third leading cause of death in the United States.

"This multinational collaboration will be one of the largest stroke genetics research projects ever launched. Recent studies in conditions such as diabetes and lupus have shown that a large sample size, such as the one we will be using, can be vital in helping to uncover genetic influences in a complex disease, so we are eager to see what genetic variants we may find for stroke and what promise these discoveries may hold for prevention and treatment," explains Steven Kittner, M.D., M.P.H., principal investigator, professor of neurology at the University of Maryland School of Medicine and a researcher at the Baltimore VA Medical Center.

"Using DNA analysis of blood samples from at least 6,000 stroke patients, we will be able to interrogate more than one million genetic variants for their association with stroke. The design and size of the study increase the chance that we may find genetic variants that were previously not suspected to be linked to stroke," says Braxton Mitchell, Ph.D., M.P.H., professor of medicine at the University of Maryland School of Medicine and leader of the multi-institutional team that will analyze the data.

With funding from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), this initiative brings together 17 different research institutions: 12 in the United States and five in Europe. The project, which should take about four years to complete, furthers the NIH efforts in the field of ischemic stroke genetics and genome wide association studies (GWAS).

"Stroke is a challenging disease to study because it can be due to a wide variety of causes and pathological processes. One important goal for this international team will be to develop standardized, validated and easily replicated methods to identify stroke subtypes, which may account for variations in stroke occurrence, severity, complications, response to therapy and recovery," explains Katrina Gwinn, M.D., NINDS project director.

Established risk factors, such as hypertension and cigarette smoking, are not sufficient to explain who will suffer from a stroke and who will be spared. Classifying strokes into subtypes using a standardized method will allow the researchers to drill down into the genetics that may be linked to a particular subgroup of stroke. In addition, the component elements leading to inclusion into or exclusion from each subgroup will be recorded, allowing for the future development of new approaches to classification. The information will be made public via the Database of Genotype and Phenotype (dbGaP).

"This consortium, led by our University of Maryland neurologists, has a unique opportunity to evaluate stroke data in a standard classification to create a resource for stroke investigators around the world for years to come," adds E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine.

Nearly 800,000 strokes occur each year in the United States. A stroke disrupts blood flow to the brain causing cells to die, increasing the risk of permanent brain damage, disability or death. Symptoms include numbness or weakness on one side of the body, sudden loss of vision, sudden confusion or trouble speaking, dizziness or loss of balance, and sudden, severe headache. A stroke can cause someone to have permanent difficulty with walking, hearing and vision, and speaking and understanding speech. Strokes can also cause emotional changes.

Certain medical factors can increase a person's likelihood of having a stroke. These include having had a previous stroke, diabetes, high blood pressure, atrial fibrillation, and heart disease. Lifestyle factors such as smoking, being overweight and drinking too much alcohol can also increase a person's risk for stroke.