Intracranial aneurysms: (epi)genetic and pathogenic factors in the circle of Willis

Abstract

Intracranial aneurysms are balloon-shaped dilations on the blood vessels of the brain, that occur in approximately 3% of the population. These aneurysms can burst and cause subarachnoid hemorrhage, a relatively rare form of stroke that predominantly affects young persons (mean age 50 years). Genetics are involved in the development of intracranial aneurysms. Previous research has shown that some areas in the DNA are linked to the development of intracranial aneurysms. The research in this thesis was focused on further characterizing these areas, since they are very large, contain many different genes and also regions that regulate whether a gene is turned ‘on’ or ‘off’ (or something in between). We have focused on these regulatory regions and discovered that the DNA that is linked to intracranial aneurysms often overlaps with such regulatory DNA regions. Therefore, it may well be that DNA that is linked to intracranial aneurysms affects the activity of genes and thereby increases the risk of developing an intracranial aneurysm. Next, we have identified six genes that have an interaction with the regulatory regions and may be regulated by these regions. Lastly, we have tested whether these regulatory DNA regions can really regulate gene activity and found that most of them can. This research provides new starting points for future research into the genetics of intracranial aneurysms. In the future we hope to be able to genetically screen individuals for their risk of developing an intracranial aneurysm, in order to be able to regularly monitor those individuals with an increased risk.