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Switzerland: Risk Assessment Are You Susceptible to Brain Aneurysms? 17 Genetic Abnormalities Show Personal Risk

Editor: Alexander Stark

By studying the genomes of hundreds of thousands of people, scientists from Unige, HUG and the University of Utrecht discovered the genetic basis of intracranial aneurysms.

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An aneurysm is a dome that usually grows at an intracerebral arterial bifurcation. The process starts when there is too much blood rubbing (in red). The growth of the dome is a natural phenomenon aimed at decreasing the friction forces (in blue) and thus allowing the vessel to heal.
An aneurysm is a dome that usually grows at an intracerebral arterial bifurcation. The process starts when there is too much blood rubbing (in red). The growth of the dome is a natural phenomenon aimed at decreasing the friction forces (in blue) and thus allowing the vessel to heal.
(Source: Unige)

Geneva/Switzerland — Nearly three percent of the world’s population is at risk of developing an intracranial aneurysm, a localized dilation of a blood vessel forming a fragile pocket. Rupture of this aneurysm results in extremely severe, and, in one-third of cases, fatal haemorrhage. In the framework of the International Stroke Genetics Consortium, a team led by the University of Geneva (Unige), the University Hospitals of Geneva (HUG) and the University of Utrecht is studying the genetic determinants of aneurysms in order to better understand the different forms of the disease and to assess individual risk.

Through the examination of the genome of more than 10,000 people suffering from aneurysms compared to that of 300,000 healthy volunteers, 17 genetic abnormalities have been identified that are notably involved in the functioning of the vascular endothelium, the inner lining of blood vessels. In addition, the scientists discovered a potential link between these genetic markers and anti-epileptic drugs, making it possible to consider the use of certain drugs in the management of the disease. These results, to be read in the journal Nature Genetics, also highlight how the wise use of large databases containing genomic and phenotypic information can advance research.

Most of these genetic abnormalities appear to be related to the functioning of the endothelial cells that line the inside of blood vessels and usually make them robust. “These cells have long been suspected of being responsible for aneurysms,” says Philippe Bijlenga, Assistant Professor in the Department of Clinical Neurosciences at Unige Faculty of Medicine and Senior Consultant at HUG Division of Neurosurgery, who led the Swiss part of this study. “We now have evidence that leads us to work on possible markers of instability that could indicate whether the aneurysm is stable, healed, or at high risk of adverse outcomes.”

In addition, this research shows that a genetic predisposition to high blood pressure and smoking play an important role in the development of an intracranial aneurysm. If these risk factors were already known from a clinical and epidemiological point of view, there now is the genetic evidence.

The scientists also made a surprising discovery: It appears that the protein structures of some of the genes they identified are linked to antiepileptic drugs. They do not yet know whether this effect is positive or negative, but it opens up the possibility for pharmacological treatments, potentially less invasive than the surgical approaches we are currently using. The scientists will now work on modelling the disease, both biologically and therapeutically, to offer physicians a medical decision support system that will help determine potential management protocols based on each person’s genetic data.

Original Article: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

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