SUPR
Genetic Polymorphisms that affect long-term outcome in aneurysmal subarachnoid hemorrhage patients
Dnr:

sens2023534

Type:

NAISS SENS

Principal Investigator:

Sajna Anand Sadanandan

Affiliation:

Umeå universitet

Start Date:

2023-03-30

End Date:

2024-04-01

Primary Classification:

30207: Neurology

Webpage:

Allocation

  • Castor /proj/nobackup at UPPMAX: 1000 GiB
  • Castor /proj at UPPMAX: 1000 GiB
  • Cygnus /proj/nobackup at UPPMAX: 1000 GiB
  • Cygnus /proj at UPPMAX: 1000 GiB
  • Bianca at UPPMAX: 2 x 1000 core-h/month

Abstract

Aneurysmal subarachnoid hemorrhages (aSAH) can result in delayed neurological deficits (DND) in patients, however there are currently no reliable methods for early prognostication of long-term outcome in these patients. Previous studies from our group (Sjöberg R et al 2015 and Johansson C et al 2022) indicated that changes in the plasma concentration of the metabolite myo-inositol may be used to predict long-term outcome. We have shown that patients with higher levels of myo-inositol on day 7 post-ictus had more favourable outcome and that changes in plasma-myo inositol levels over the first 10 days post-ictus could be used to predict outcome after a year (Johansson C et al 2022). A recent study (Weston E et al 2022) that looked into the genetic determinants of plasma inositol status in adult humans has identified 4 functionally relevant SNPs in the SLC5A11 gene. A few other SNPs in genes such as MTDH, LAPTM4B and ZP2 were also identified in this study. Unfavourable outcome in aSAH patients is primarily mediated by 3 pathophysiological processes; rebleeding, hydrocephalus and cerebral vasospasm. Vasospasm typically occurs days 5-10 post the initial hemorrhage which roughly correlates with the changes in myo-inositol levels. It would hence also be interesting to look at the correlation between genetic polymorphisms, myo-inositol levels, radiologically verified vasospasm and long-term outcome in these patients. We have genomic data from patients who were treated for aSAH at the Norrlands University Hospital and intend to use this data to perform our analysis. Approved by the ethics committee at Umeå University. We intend to use your platform for analysis of the genomic data and imputation of further SNPs. The main objectives of our current project are to 1. To identify genetic polymorphisms in relevant genes (ex SLC5A11) that are associated with the initial myoinsotol levels in subarachnoid patients 2. To identify genetic polymorphisms in relevant genes (ex SLC5A11) that are associated with changes in the myoinositol levels post-ictus in subarachnoid patients 3. To identify genetic polymorphisms in relevant genes that are associated with 1,2 and cerebral vasospam in subarachnoid patients