New research links dozens more genes to stroke, identifies potential drug targets

Researchers at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) are part of an international team that has identified 61 additional genetic loci associated with stroke and six genes that are potential targets for drug therapy for prevention. or stroke treatment. Findings published on September 28 in Nature, based on data from 2.5 million people of five different backgrounds, more than 200,000 of whom had suffered a stroke. The study was conducted by members of the GIGASTROKE consortium.

Stroke is the second leading cause of death worldwide, accounting for approximately 12% of all deaths and the leading cause of years of life lost or life with disability. Loci are the physical locations of genes on the chromosomes of cells and are called genetic street addresses.

Nature article co-author Sudha Seshadri, MD, professor of neurology at the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio, is the founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. She chairs the CHARGE Neuroscience Working Group, an international consortium that contributed to the new findings.

“The population studied in this work has a fairly global representation, including Africa, South Asia, East Asia, Europe and Latin America,” Seshadri said. “Interestingly, one group that remains underrepresented is the US Hispanic population, so there’s still work to be done.”

Stroke is a major risk factor for dementia, and there is significant overlap between the conditions, Seshadri said. A stroke affects small vessels, the endothelial cells that line them blood vesseland cells called pericytes, which are important for the formation of blood vessels and other functions. Vascular cognitive impairment and dementia also affect small vessels, endothelial cells and pericytes, Seshadri said.

“There is a common biology between stroke and dementia, and there are research methods used in this project to study the genetics of stroke that will make us stronger in studying dementia,” said study co-author Claudia Satizabal, Ph.D., associate professor of population health sciences at UT Health San Antonio and a Glenn Biggs Institute investigator.

Co-author Muralidharan Sargurupremraj, Ph.D., who worked with colleagues in Bordeaux, France on the global initiative before coming to the Glenn Biggs Institute, said the large-scale project showed the utility of using multiple methods to “go from loci, from genetic variation, to identifying molecules and pathways , which can be drug targets a stroke.”

Seshadri noted that drug targets currently known for Alzheimer’s disease and related dementias have not resulted in effective therapies. “I really believe that discovering new biology and looking for it is one of the most promising ways to find new drug targets and treatments for dementia,” she said.

Over the next 10 years, she said, dementia Clinical care, fueled by research like the GIGASTROKE findings, “will progress to taking a patient’s blood sample and seeing a person’s genetics, and thus understanding what is going on in the brain and providing targeted treatment.”