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Kidney Week

Abstract: TH-PO646

Polygenic Burden for Hypertension, Stroke, and Intracranial Aneurysm in Deceased Kidney Donors

Session Information

  • Transplantation: Basic
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Collins, Kane Edmund, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Gilbert, Edmund H., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Benson, Katherine A., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • Lord, Graham M., King's College London, London, London, United Kingdom
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
Background

Intracranial Haemorrhage (ICH) and stroke are common causes of death among kidney donors, but the genetic factors involved are poorly understood. Polygenic burden for a trait can be calculated by generating a Polygenic Risk Score (PRS) which estimates the cumulative effect of common genetic variation on an individual’s disease status. Previous studies have found that PRS for ischemic stroke offer predictive performance similar to clinical risk factors. Here we investigate the role of polygenic burden in determining donor cause and age of death.

Methods

We utilised 2122 genotyped kidney transplant donor-recipient pairs from across the UK and Ireland. We calculated PRSs for stroke, Intracranial Aneurysm (IA) and hypertension using large published GWASs of European ancestry. We compared PRSs between the donors who died of intracranial haemorrhage (DDICH) (1,303 individuals) and controls, as well as donors who did not die of ICH. We investigated whether kidneys that came from individuals with high polygenic risk (defined as top 20% of distribution) performed differently from lower risk kidneys (bottom 80%) when transplanted into recipients.

Results

DDICH had significantly higher PRSs for hypertension, stroke, and IA than controls (p-values 1.0e-13, 1.2e-11, and 0.028 respectively), but also than the donors who did not die of ICH (p-values 2.9e-9, 2.3e-4, and 0.41). The risk of death from ICH was 9% greater in individuals with high polygenic risk for hypertension (OR: 1.09, p: 0.015). Similarly, for donor age of death, polygenic risk for hypertension had an Odds Ratio (OR) of 12.2 (p-value 0.002). Polygenic risk for each trait in donor kidneys did not have a statistically significant impact on graft survival.

Conclusion

These observations support the hypothesis that DDICH carry an increased burden for traits related to stroke. This results in a greater risk of death from ICH and a younger age of death. These PRSs are similarly predictive to established clinical risk factors. Kidneys that come from donors with high polygenic risk for all traits do not have different graft function or survival from low risk kidneys. PRSs can distinguish DDICH from the general population. These findings could have utility in testing relatives of DDICH to determine if they share the same risk for ICH.

Funding

  • Government Support – Non-U.S.