Worldwide study triples number of known genetic risk factors for stroke


By Will Sansom

Research co-author Dr. Sudha Seshadri of UT Health San Antonio’s Glenn Biggs Institute predicts that the study will also be a boon for dementia research

SAN ANTONIO (March 12, 2018)—A landmark international study of DNA samples from 520,000 individuals worldwide—including 67,000 affected individuals—identified 22 new genetic risk factors for stroke. Sudha Seshadri, M.D., of UT Health San Antonio, is senior co-author of this largest genetic study of stroke to date. Nature Genetics published the results online today [March 12].

Previously, only 10 genetic risk factors had been identified for stroke.

Dr. Seshadri, founding director of the Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases at UT Health San Antonio and holder of the university’s Robert Barker Distinguished University Chair, said the identification of genetic regions that are strongly correlated to stroke will increase potential targets for stroke drug development.

A chief aim of the Glenn Biggs Institute is to identify novel risk factors and groundbreaking treatments for dementia, and the study provides excellent fodder for investigations along that line, Dr. Seshadri said.

“Understanding these newly identified risk factors for stroke should also enable us to find novel treatments for dementia,” Dr. Seshadri said. “Vascular disease in the brain—a series of strokes—can lead to dementia.”

The study identified novel genetic risk factors for all major subtypes of ischemic stroke. An ischemic stroke occurs when a blood vessel supplying the brain is blocked. About 80 percent of strokes are ischemic.

The study found the largest correlation between genetic risk factors and blood pressure. Hypertension is a major risk factor for stroke.

Vascular health is important for brain function. The brain does not store energy and requires a constant supply of blood and oxygen, as well as blood glucose. “Any disruption can lead to cognitive problems,” Dr. Seshadri said. “The most obvious example of that is stroke. There is a deficit in the blood supply and that is associated with very obvious changes in cognitive function.”

Dr. Seshadri and colleagues with the Framingham Heart Study in Massachusetts observed that having higher ideal cardiovascular health scores on an American Heart Association scale was associated with a lower risk of developing Alzheimer’s dementia.

“What is good for your heart also seems to be very good for your brain,” she said. “It is important to adopt heart-healthy behaviors such as a nutritious diet and regular, adequate exercise.”

The stroke risk factors study was conducted by members of MEGASTROKE, a large-scale international collaboration launched by the International Stroke Genetics Consortium. MEGASTROKE members include research groups from Germany, France, the United Kingdom, Japan, the United States, Iceland, Spain, Switzerland, Italy, Belgium, the Netherlands, Denmark, Sweden, Norway, Finland, Estonia, Poland, Singapore, Australia and Canada.

The study received financial support from multiple sources including the National Heart, Lung and Blood Institute (NHLBI) and the National Institute for Neurological Diseases and Stroke (NINDS).

Formerly of Boston University, Dr. Seshadri is a senior investigator in the Framingham Heart Study and leads the neurology working group within several international consortia.

The Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases was announced by William L. Henrich, M.D., MACP, president of UT Health San Antonio, in September 2015. Named in honor of San Antonio businessman Glenn Biggs, the Biggs Institute was established to address the community’s need of a comprehensive center for neurodegenerative disease research and care. Community donors gave more than $50 million to stand up the institute. Dr. Seshadri, internationally respected dementia research leader from Boston University, began duties Dec. 1, 2017, as founding director of the Glenn Biggs Institute.

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