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Kidney Week

Abstract: PO2078

Polygenic Burden for Intracranial Aneurysm and Hypertension in Deceased Kidney Donors Who Died of Intracranial Haemorrhage

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Collins, Kane Edmund, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Gilbert, Edmund H., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland

Group or Team Name

  • Human Genetic Variation Research Group
Background

A polygenic risk score (PRS) estimates the cumulative effect of common genetic variation on an individual’s disease status. It is calculated by summing up all the effect alleles present in the individual, weighted by the effect size, as measured in a GWAS. Intracranial haemorrhage is a common cause of death among kidney donors, but limited research has been done to investigate polygenic burden for intracranial aneurysm (IA) and hypertension in deceased transplant donors.

Methods

Our data consisted of 2,122 genotyped donor-recipient pairs from the United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and 5,519 controls from the 1958 British Birth Cohort and UK Blood Service. We created polygenic risk scores for IA and hypertension using published GWAS summary statistics from 7,495 cases and 71,934 controls for IA and 76,566 cases and 206,305 controls for hypertension. We investigated the difference in PRS between the UKIRTC donors who died of intracranial haemorrhage (1,303 individuals) and the controls while adjusting for covariates of sex and the first 4 principal components.

Results

We found that the IA PRS explained 4.1% of the variance between case and control status (p-value: 9.6 x 10-39). The odds ratio on the phenotype for those in the lowest demi-decile of the IA PRS was 0.52 (95% CI: 0.34-0.82) compared to 2.8 (1.9-4.0) for those in the highest demi-decile. Similarly, the PRS for hypertension explained 1% of the variance (p-value: 7.5 x 10-10) and the corresponding odds ratios were 0.68 (CI: 0.46-1.0) and 1.5 (1.1-2.3) for those in the lowest and highest demi-deciles respectively.

Conclusion

PRSs for IA and hypertension based on these data appear to explain 4% and 1% respectively of the variance in case-control status between kidney donors who have died of intracerebral haemorrhage and controls. These observations could have utility in testing relatives of donors who died of intracranial haemorrhage to determine if they share the same risk for intracerebral haemorrhage and if so to may be useful in advising regarding screening or other precautions to minimise their risk of intracerebral haemorrhage. These observations need to be confirmed in other cohorts. Further studies using similar approaches could investigate other causes of death among kidney donors.

Funding

  • Government Support – Non-U.S.