Abstract: SA-PO751
Polygenic Effects on the Risks of Intracranial Aneurysms Among Patients with ADPKD
Session Information
- Genetic Diseases: Cystic - Genetic Analysis and Extrarenal Manifestations
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Osman, Shohdan Hussein Mohamed, Beaumont Hospital, Dublin, Ireland
- Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
- Collins, Kane Edmund, Centre for Research Training in Genomics Data science, Dublin, Ireland
- Benson, Katherine A., Royal College of Surgeons in Ireland, Dublin, Ireland
- Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Dublin, Ireland
- Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
Background
Patients with autosomal dominant polycystic kidney disease ADPKD are at an increased risk of intracranial aneurysms (IA). Although there is an ongoing debate on who to screen, current strategies do not provide a personalised evaluation on risk of development and progression of IA. In this study, we aimed to identify the association of risk of IA in patients with ADPKD and genome-wide polygenic scores (PGS).
Methods
All adult ADPKD patients enrolled in the Irish Kidney Gene Project who underwent cerebral image screening for IA were included. Using previously published array SNP genotype data, we created PGS for six traits (hypertension (HTN) albuminuria, total kidney volume (KV), intracranial aneurysm (IA), and stroke, and glomerular filtration rate(GFR). Using PRSice2 software, PGS were calculated, and each trait was quantified categorically into three groups (high PGS >70%, average PGS 31%–70%, and low PGS <30%). To identify potential IA-specific risk factors, the polygenic effects of each GPS trait were compared between patients with and without IA using logistic regression.
Results
A total 226 participants (mean age 57.1 ± 14.4 years, 59.7% female) were assessed for IA-specific genomic risk stratification. 213 (88%) patients had hypertension, and 140 patients progressed to kidney failure at mean age 49.4 ± 10.4 years. Family history of IA was confirmed in 75 (33.1%) patients. Forty-seven (20.8%) patients had intracranial aneurysms, with 31.9% having multiple IA. Compared to the average (31%–70%) PGS distribution for each trait, the distribution of high or low PGS did not have a differential impact on the risk of IA development in patients with ADPKD.
Conclusion
Our current method did not identify a significant polygenic effect for the risk of IA in ADPKD patients, possibly due to the small sample size. To test this hypothesis, a larger study would be needed.