Abstract: SA-PO0584
Genetic and Clinical Profiles of ADPKD in Two Population-Based Cohorts
Session Information
- Cystic Kidney Diseases: Clinical Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Elbarougy, Doaa E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Yang, Hana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- McDonnell, Shannon K., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Frank, Jacob A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ma, Jun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Cruz, Conrad, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Dahl, Neera K., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Larson, Nicholas B., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Most ADPKD cases are caused by PKD1 or PKD2. Additional genes have been recently linked to atypical cases, but some ADPKD cases remain genetically unresolved. We studied two population-based cohorts with whole-exome sequencing (WES) and clinical/imaging data to characterize the genetic spectrum and phenotypic variability of ADPKD.
Methods
We studied 52,786 Mayo Clinic Biobank (MCBB) and 82,445 Tapestry participants. We screened ADPKD candidates via ICD-9/10 kidney cyst codes and screened for truncating (T) and nontruncating (NT) variants in PKD1, PKD2, and only T in the minor ADPKD genes. Patient charts and imaging were reviewed.
Results
An ADPKD-spectrum was confirmed in 159 (0.3%) MCBB and 212 (0.26%) Tapestry participants. In MCBB, PKD1-T, PKD1-NT, PKD2, and minor gene variants accounted for 31%, 15%, 14.5%, and 12% of cases, respectively. In Tapestry, these genes accounted for 39%, 24.5%, 13%, and 7%. The remainder (27.6% in MCBB; 17.5% in Tapestry) had no identified causative variants. Genotype correlated with disease severity: PKD1-T variant carriers had larger htTKV than other gene carriers (Figure 1). After adjusting for age (centering at the overall mean of 60.6 years), the estimated mean eGFR was 34 mL/min/1.73m2 in MCBB and 54 mL/min/1.73m2 in Tapestry (p<0.001) suggesting Tapestry has more mild patients.
Population-wide screening for T variants in minor ADPKD genes showed reduced penetrance; for each gene, carriers developed >10 cysts in <50% of cases with enhanced CT or MR imaging (Table 1).
Conclusion
Using population-based genetic and phenotypic data, we captured a full ADPKD spectrum and gene-dependent variability. Our findings indicate high penetrance for PKD1/PKD2 but variable penetrance of the minor genes. These data highlight the value of population approaches and the potential to identify additional ADPKD genetic causes and modifiers.
Funding
- NIDDK Support