Abstract: FR-PO935
Polygenic Burden as a Predictor of Age at Onset of ESRD
Session Information
- CKD: Epidemiology, Risk Factors, Prevention - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2201 CKD (Non-Dialysis): Epidemiology‚ Risk Factors‚ and Prevention
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
There are a large number of well-established clinical risk factors for age of onset of ESRD including diabetes, hypertension, heart disease, and obesity. Patients with CKD have also been shown to have a significant enrichment of rare variation in genes related to kidney disease. However, little research has been done to investigate the role of burden from common genetic risk factors on age of onset of ESRD, as quantified using polygenic risk scores (PRS) which estimates the cumulative effect of common genetic variation on an individual’s disease status. Here, we investigate the association between polygenic burden for hypertension, albuminuria, eGFR and kidney volume (KV) and age of onset of ESRD.
Methods
We utilised 2,122 genotyped kidney transplant recipients from across the UK and Ireland (UKIRTC) and 5,519 ancestry matched controls. For these transplant recipients, we used age of transplant as a proxy for age of onset of ESRD. We also used 190 genotyped Irish individuals with Polycystic Kidney Disease (PKD). We calculated PRSs for each trait using large published GWASs of European ancestry. We then investigated the relationship between age of onset of ESRD and polygenic burden in each cohort separately and then together.
Results
The UKRITC recipients had a higher polygenic burden than healthy controls for reduced eGFR (p-value 0.006) and albuminuria (p-value 0.056). The PKD patients also had increased burden for albuminuria (p-value: 0.003). Taken together, all the patients from the two cohorts had higher polygenic burden for albuminuria and reduced eGFR than healthy controls (p-values: 0.003, 0.01 respectively). We compared age of onset of ESRD between individuals in the top 20% of polygenic risk for each trait to those in the bottom 80% and found an Odds Ratios (OR) of 3.75 for hypertension (p-value: 0.052) and 0.261 for reduced eGFR (p-value: 0.051).
Conclusion
These observations support the hypothesis that individuals with CKD have higher common variant burden for traits related to reduced kidney function and that polygenic burden is a borderline statistically significant predictor of age of onset of ESRD. A larger sample size may verify the magnitude of this effect. If replicated in a larger dataset, these findings could lead to modifications of screening and treatment of ESRD.
Funding
- Government Support – Non-U.S.