ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO755

Population Analyses to Determine Genetic Causes of Kidney Cysts

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Yang, Hana, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Bublitz, Josh T., Mayo Clinic, Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Rochester, Minnesota, United States
  • Larson, Nicholas B., Mayo Clinic, Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Rochester, Minnesota, United States
  • Elbarougy, Doaa Emadeldin Shafik, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Schauer, Rachel S., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease with two major and at least seven minor genes. Information on the phenotypic penetrance of variants in these genes is biased as their analysis is usually limited to known ADPKD populations. In addition, the full genetic causes of kidney cysts may not be fully identified because kidney clinic patients are usually screened. Large populations with detailed clinical/imaging data and whole exome sequencing (WES) allow genotype- and phenotype-first approaches to clarify kidney cyst genetics. The Mayo Clinic Biobank (MCBB; n=52,865) is a population-based cohort with clinical records and WES that can allow these approaches to be employed.

Methods

In a phenotype-first approach, ICD9/10 codes and other diagnoses of kidney cysts have been employed to identify ADPKD and kidney cyst populations in the MCBB. WES data associated with these groups are being screened for likely causative variants. In the genotype-first approach, we are screening for loss-of-function (LoF) and known pathogenic variants in the ADPKD genes in MCBB participants. Examination of clinical records and imaging will determine the cystic disease penetrance of these variants.

Results

Using 15 renal/hepatic cyst related ICD codes, we identified a total of 1,093 individuals in the MCBB (2.08%). Of these, 184 were coded as ADPKD (0.35% in the MCBB), 579 with other cystic kidney phenotypes (1.10%), 294 with a single cyst (0.56%), and 36 with just liver cysts (0.07%). Analysis of the MCBB for patients previously diagnosed with ADPKD identified 108 patients; reassuringly, 101 (93.5%) were also found with the ADPKD ICD codes. MCBB also contains 50 patients previously diagnosed with kidney cysts; 26 had cystic ICD codes. Utilizing CPT codes, we have found that 1,013 (92.7%) of these patients have available imaging data (MRI, CT, or ultrasound). Manual inspection is underway to verify the phenotypes, and genetic variants from 341 PKD/ciliopathy genes are being retrieved for these patients. LoF and known pathogenic variants in all ADPKD genes are also being identified in the whole MCBB for the genotype-first analysis.

Conclusion

Population-based analyses can better explain the genetics of kidney cysts and penetrance of ADPKD genes, and the MCBB is ideally suited for this analysis.

Funding

  • NIDDK Support