In the UK, approximately 8 per 100,000 people suffer from subarachnoid hemorrhage (SAH) each year. The most common cause of SAH is the rupture of an intracranial aneurysm. A third of the patients with aneurysmal SAH (aSAH) die , a third of those who survive suffer from complications. Iron accumulation in the brain has gained more interest as a key factor in the development of delayed cerebral ischemia (DCI). DCI is a major cause of poor outcomes in patients suffering from aSAH. The exact mechanisms of DCI development are still unclear, which also complicates the development of preventative treatments. Using data from the UK Biobank, this study aims to investigate the relationship between iron deposition in the brain after aSAH and poor clinical outcomes. This association will be tested with the use of single nucleotide polymorphisms (SNPs) that affect serum iron. If an association is found between SNPs that influence serum iron and poor patient outcomes after aSAH, we can assume that this effect is mediated by a difference in iron deposition in the brain.
Summary-level data from a genome-wide meta-analysis of iron status biomarkers will be used to select SNPs associated with serum iron. Because standard outcome scores like: GOS or mRS are not available in UK Biobank, a different score will be used. Outcome will be assessed using psychomotor reaction time, since this is a measure of cognitive performance, and varies significantly between a control population and aSAH patients . This definition was also used by a Genome-wide association study (GWAS) researching clinical outcome after aSAH (Gaastra et al., 2022). Combining the publicly available GWAS statistics and participant data from the UK Biobank it is possible to test for an association between iron and poor clinical outcome after aSAH. This leads to the research question: what is the effect of iron on the risk of poor clinical outcome after subarachnoid hemorrhage in participants of the UK Biobank .