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Frequency of ClinVar Pathogenic Variants in Chronic Kidney Disease Patients Surveyed for Return of Research Results at a Cleveland Public Hospital.

ABSTRACT: Return of results is not common in research settings as standards are not yet in place for what to return, how to return, and to whom. As a pioneer of large-scale of return of research results, the Precision Medicine Initiative Cohort now known of All of Us plans to return pharmacogenomic results and variants of clinical significance to its participants starting late 2019. To better understand the local landscape of possibilities regarding return of research results, we assessed the frequency of pathogenic variants and APOL1 renal risk variants in a small diverse cohort of chronic kidney disease patients (CKD) ascertained from a public hospital in Cleveland, Ohio genotyped on the Illumina Infinium MegaEX. Of the 23,720 ClinVar-designated variants directly assayed by the MegaEX, 8,355 (35%) had at least one alternate allele in the 130 participants genotyped. Of these, 18 ClinVar variants deemed pathogenic by multiple submitters with no conflicts in interpretation were distributed across 27 participants. The majority of these pathogenic ClinVar variants (14/18) were associated with autosomal recessive disorders. Of note were four African American carriers of TTR rs76992529 associated with amyloidogenic transthyretin amyloidosis, otherwise known as familial transthyretin amyloidosis (FTA). FTA, an autosomal dominant disorder with variable penetrance, is more common among African-descent populations compared with European-descent populations. Also common in this CKD population were APOL1 renal risk alleles G1 (rs73885319) and G2 (rs71785313) with 60% of the study population carrying at least one renal risk allele. Both pathogenic ClinVar variants and APOL1 renal risk alleles were distributed among participants who wanted actionable genetic results returned, wanted genetic results returned regardless of actionability, and wanted no results returned. Results from this local genetic study highlight challenges in which variants to report, how to interpret them, and the participant's potential for follow-up, only some of the challenges in return of research results likely facing larger studies such as All of Us.

SUBMITTER: Crawford DC

PROVIDER: S-EPMC6931908 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Frequency of ClinVar Pathogenic Variants in Chronic Kidney Disease Patients Surveyed for Return of Research Results at a Cleveland Public Hospital.

Crawford Dana C DC Lin John J Cooke Bailey Jessica N JN Kinzy Tyler T Sedor John R JR O'Toole John F JF Bush William S WS

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 20200101

Return of results is not common in research settings as standards are not yet in place for what to return, how to return, and to whom. As a pioneer of large-scale of return of research results, the Precision Medicine Initiative Cohort now known of All of Us plans to return pharmacogenomic results and variants of clinical significance to its participants starting late 2019. To better understand the local landscape of possibilities regarding return of research results, we assessed the frequency of ...[more]

PMID: 31797629

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Project description:BackgroundThe kidney biopsy is the gold standard for diagnosing glomerular diseases. Large-scale, epidemiologic studies describing the prevalence of kidney diseases are lacking, especially in the United States. We aimed to determine the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise.MethodsWe identified all patients with a native kidney biopsy performed or reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, sex, race, and location to determine epidemiologic trends.ResultsOf >9600 patients, we excluded transplant and donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46% female patients. Self-reported racial demographics included 73% White, 22% Black, 3% multiracial, and 2% Asian background, with 5% Hispanic. Common diagnoses were: FSGS (n=633, 15%), diabetic kidney disease (DKD) (n=602, 15%), IgA nephropathy (n=319, 8%), lupus nephritis (LN) (n=289, 7%), pauci-immune glomerulonephritis (n=275, 7%), membranous nephropathy (n=211, 5%), and amyloidosis (n=110, 3%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those aged >70 years were more likely to have FSGS, whereas those <45 years were more likely to have IgA nephropathy or LN. Males were more likely to have FSGS or IgAN, and less likely to have LN. Black patients were more likely to have FSGS, DKD, or LN. Hispanic patients were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum before and during the COVID-19 pandemic.ConclusionOur study catalogs the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials, and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States.

Dataset Information

Frequency of ClinVar Pathogenic Variants in Chronic Kidney Disease Patients Surveyed for Return of Research Results at a Cleveland Public Hospital.

Publications

Frequency of ClinVar Pathogenic Variants in Chronic Kidney Disease Patients Surveyed for Return of Research Results at a Cleveland Public Hospital.

Similar Datasets

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