Review of genetic analyses for sex differences in intracranial aneurysms

Abstract

An intracranial aneurysm (IA) is a dilation of an artery in the brain that fills with blood. They have a chance to rupture from the pressure and cause blood to spill into the surrounding tissue causing a subarachnoid haemorrhage (SAH). IAs are also relatively common among the general population with an occurrence of 3 to 5%. SAH causes severe health issues in a large portion of patients such as permanent disability and has a high mortality rate. This means that although the amount of IAs that rupture is low, it affects the patient's health severely when it does. However, current treatment still has many limitations and IAs go unnoticed until it ruptures in most cases. That’s why it is important to further improve the assessment and treatment of IA.

To better understand IAs, two topics are especially important: heritable factors (genetic background) and differences between males and females. People with first or second-degree family members who already have suffered from an SAH are more likely to develop IAs and the occurrence of IAs in this subgroup is 7%. Factors of IAs such as risk of development, age at which the IA develops and location in the brain at which the IAs occur, are all found to be influenced by genetics. Some of the genetic factors that cause IAs also influence other health issues which are also influenced by genetics, such as Ehlers-Danlos syndrome. Overall, these findings mean that IAs are influenced by genetics. Regarding sex differences, females are more likely to develop an IA or an SAH. Besides that, factors of IAs such as the location of the IA or the number of IAs that have developed are also found to be different between males and females. Although information is known about the genetic background and sex differences separately, the combination is currently severely understudied. It is as of yet unknown how and to what extent the genetic background influences and causes the sex differences.

However, multiple options to study the genetic background of sex differences are available and since these options could be very useful in better understanding IAs, this review aims to provide an overview of current available methods. Three categories are described in this review. The first category is finding new genetic association studies which look for new genes that cause IAs. The second category is shared biology, meaning to look if there are any similarities in genetic background when comparing two diseases with each other. The third category is risk prediction, meaning looking at a person’s DNA and predicting the risk of developing an IA. By doing these different methods for a male group and female group separately, differences between the two groups might be found.

The methods that are described in the paper and summarized in the paragraph above, have the potential to provide insights that are beneficial to better understanding IAs but could also aid the development of the prevention, assessment and treatment of IAs. Thereby lowering the number of patients and severe health issues that IAs can cause. Despite the methods being promising, it is vital to develop genetic studies carefully and keep in mind limitations. It is important to choose the right method and to understand the results well. Besides that, the methods and tools that can be used for genetic studies are being improved very quickly. This means new methods are being developed constantly and staying on top of those developments should be a priority.