Genetic risk factors for brain aneurysms identified in large-scale study

A large study has identified for the first time three genetic risk factors for brain aneurysms, bulging blood vessels in the brain that can cause fatal strokes when they rupture. Since patients with a brain aneurysm can show no symptoms prior to having a stroke, being able to identify those at risk could save lives through allowing early detection and repair of aneurysms. The study was conducted by Murat Gunel, professor of neurosurgery and neurobiology, and Richard Lifton, Sterling Professor and chair of genetics, both at the Howard Hughes Medical Institute, Yale, US, and is published in Nature Genetics. Commenting on the work, Professor Lifton said that it 'starts to put us on a path toward being able to identify patients who should be screened for brain aneurysms'.

In the study, the genomes of 2000 brain aneursym patients and 8000 healthy volunteers from Finland, Japan and the Netherlands were examined. The researchers found three genes with a variation more frequent in aneurysm patients than in healthy controls. There are normally several different versions, or alleles, of every human gene. This variation leads to differences in hair or eye colour, for instance, but can also affect susceptibility to disease. No differences were observed between nationalities in the study, showing that the variations are common to diverse groups.

One of the variant alleles detected is SOX17, a gene known to be involved in the development and repair of blood vessel walls. The risk of a brain aneurysm increases with the presence of each variant; individuals with all three are predicted to have a threefold increase in risk of brain aneurysm. Screening could therefore be beneficial for people who possess the variant genes. Although some people experience a splitting headache as an aneurysm develops, many can only be identified by a brain scan. An aneurysm can lead to blood clots or rupture and bleed into the brain, causing a stroke. This can be fatal and survivors frequently sustain lasting brain damage.

The discovery may also lead to advances in the understanding and treatment of brain aneurysms, by examining in more detail the functions of the three genes. 'These variations may interfere with the ability to produce cells that repair damage to the blood vessels, suggesting a path forward for developing new approaches to prevention', Gunel said.

Andrea Lane, spokesperson for the Stroke Association, praised the study but cautioned that 'the main issues which cause aneurysms to continue to worsen are related to our lifestyle choices, for example smoking and drinking, and the genetic influence remains small in comparison.'