Scientists discover new genetic variant that increases the risk of stroke

A genetic variant that increases the risk of a common type of stroke has been identified by scientists in a study published online in Nature Genetics. This is one of the few genetic variants to date to be associated with risk of stroke.

Stroke is the second leading cause of death worldwide (more than 10% of all deaths, and over six million deaths annually), and also in developed countries is a major cause of chronic disability. As the world’s populations age the impact of stroke on wellbeing is likely to increase further.

Several different mechanisms underlie strokes. One of the most common types is when blood flow is impaired because of a blockage to one or more of the large arteries supplying blood to the brain – large artery ischemic stroke. This accounts for over a third of all strokes.

Researchers from Oxford University and St George’s, University of London, working with scientists from Europe, America and Australia, in one of the largest genetic studies of stroke to date, compared the genetic make-up of 10,000 people who had suffered from a stroke with 40,000 healthy individuals. The study was funded by the Wellcome Trust.

The researchers discovered an alteration in a gene called HDAC9 which affects a person’s risk of large artery ischemic stroke. This variant occurs on about 10 per cent of human chromosomes. Those people who carry two copies of the variant (one inherited from each parent) have nearly twice the risk for this type of stroke compared to those with no copies of the variant.

The protein produced by HDAC9 is already known to play a role in the formation of muscle tissue and heart development. However, the exact mechanism by which the genetic variant increases the risk of stroke is not yet known. A better understanding of the mechanism could lead to new drugs to treat or prevent stroke; however, the researchers stress that this is still some way off.

The researchers went on to show that the new variant does not have the same effect on the risk of other types of stroke which include bleeding in the brain (haemorrhagic stroke).

Professor Peter Donnelly, Director of the Wellcome Trust Centre for Human Genetics in the University of Oxford, who co-led the study, says:

"Our study shows that the different subtypes of stroke could involve quite different genetic mechanisms. This is really fascinating, and if it holds up more generally, will move us closer to personalised medicine, where treatments and preventions can be tailored more precisely to individual patients."

"Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke", The International Stroke Genetics Consortium and the Wellcome Trust Case Control Consortium 2. Nature Genetics (2012) doi:10.1038/ng.1081.