The ROAR-DNA project represents a breakthrough in the study of intracranial aneurysms, combining large-scale genetic analysis with clinical ambition to transform patient care. Based at University Hospital Southampton, the study uses whole-genome sequencing (WGS) to identify who is at risk of developing aneurysms, who requires treatment, and which biological pathways may hold the key to new therapeutic discoveries.
Understanding Genetic Risk Factors
Intracranial aneurysms are often sporadic, yet a significant familial component exists. Research has shown that 16.4% of patients have a parent or sibling who has also been affected. Despite this, UK screening guidelines currently extend only to those with two affected first-degree relatives. This limitation means that even among individuals carrying high-risk genetic variants, fewer than 10% are eligible for screening. Without a reliable genetic test, clinicians rely on lifelong MRI, an approach that is expensive and not feasible for population-level prevention.
Building a Comprehensive Screening Model
ROAR-DNA aims to address this limitation through comprehensive genetic risk modelling based on both rare and common variants. The study will collect DNA from 6,000 participants, with 1,000 individuals showing extreme phenotypes undergoing full WGS. These will be combined with existing data from 1,500 publicly available cases and 300,000 healthy controls. This dataset provides the statistical power needed to detect subtle genetic differences associated with both the formation and rupture of aneurysms. The rare variants identified through sequencing will then be incorporated into a customised genotyping array, which will be used to analyse the remaining 5,000 ROAR-DNA participants and more than 3,000 patients from the ongoing GO-SAH study of ruptured aneurysms.
The study has three major aims. The first is to predict aneurysm formation, enabling targeted screening of individuals most at risk. The second is to predict rupture risk, improving treatment decisions and potentially saving lives. The third is to reveal the molecular mechanisms underlying vascular instability, which could lead to the development of targeted drug therapies.
Advancing Future Treatments for Brain Aneurysms
By linking comprehensive genetic data with long-term national healthcare records, the project seeks to provide patients and physicians with accurate, actionable information. The first results of the study will be released in the first half of 2026.
Reference
The Risk of Aneurysm Rupture Study. Available at: https://roarstudy.co.uk/roar-dna-3. Last accessed: 24 October 2025.
