Genome-Wide Study Elucidates 22 New Stroke Risk Factors
Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. And now, after analyzing DNA samples from hundreds of thousands of stroke victims, an international research consortium has discovered a number of new genetic risk factors.
Researchers carrying out the MEGASTROKE study studied the DNA of more than 520,000 people from around the world, comparing the genes of those who had suffered different types of strokes with healthy volunteers.
MEGASTROKE members include research groups from Germany, France, the U.K., Japan, the U.S., Iceland, Spain, Switzerland, Italy, Belgium, the Netherlands, Denmark, Sweden, Norway, Finland, Estonia, Poland, Singapore, Australia, and Canada.
The group identified 22 new genetic risk factors for stroke, tripling the amount of gene regions known to affect stroke risk. The discovery that could yield a better understanding of stroke mechanisms and lead to more drug targets for stroke therapy.
Around a third of the newly-discovered genetic variants – different versions of a gene – are thought to increase stroke risk by increasing a person’s blood pressure, while the remainder appear to increase the risk of a stroke in completely new ways.
One specific gene increased a person’s risk of
two very different types of stroke; haemorrhagic stroke – where a blood vessel bursts and bleeds into the brain – and ischaemic stroke – in which the blood supply to the brain is blocked, for example by a blood clot.The researchers believe that this discovery could pave the way for new drugs to help reduce the risk of a person suffering from both of these common types of stroke.
“Because the extent to which individual variants modify stroke risk is very small, it required a large number of subjects to discover these variants,” said co-lead author Professor Martin Dichgans, director of the Institute for Stroke and Dementia Research at the Ludwig-Maximilians-University, Germany.
“Our group has leveraged extensive datasets set up by numerous researchers over the past few years.”
“We can’t overstate the importance of international collaboration across different ethnic origins when studying genetics of complex, common diseases like stroke. This large-scale collaboration across continents has been a game changer,” added co-lead author Professor Stephanie Debette, from the University of Bordeaux and Bordeaux University Hospital, France.
The researchers further found that the genes they identified are enriched in drug targets for antithrombotic therapy, used to re-open occluded blood vessels in patients with acute stroke or to prevent vascular events including stroke.
“These findings illustrate the potential of genetics for drug discovery,” said Dr. Bradford Worrall, a researcher at the University of Virginia School of Medicine.
“Vascular disease in the brain — a series of strokes — can lead to dementia,” Dr. Seshadri said. “Understanding these newly identified risk factors for stroke should also enable us to find novel treatments for dementia.”
