Derivation and Validation of Genome-Wide Polygenic Score for Urinary Tract Stone Diagnosis

Details

• Personal Author:
  Chaudhary K ; Chaudhry F ; Coca SG ; Damrauer SM ; Do R ; Duy PQ ; Forrest I ; Glicksberg BS ; Gupta M ; He JC ; Jaladanki S ; Judy R ; Kapoor A ; Klarin D ; Nadkarni GN ; O'Hagan R ; Paranjpe I ; Paranjpe M ; Pfail J ; Tsao N ; Vaid A
• Corporate Authors:
  Mount Sinai. Charles Bronfman Institute of Personalized Medicine. Genomics Team ; Regeneron Genetics Center. Regeneron Genomics Team
• Description:
  Urinary tract stones have high heritability indicating a strong genetic component. However, genome-wide association studies (GWAS) have uncovered only a few genome wide significant single nucleotide polymorphisms (SNPs). Polygenic risk scores (PRS) sum cumulative effect of many SNPs and shed light on underlying genetic architecture. Using GWAS summary statistics from 361,141 participants in the United Kingdom Biobank, we generated a PRS and determined association with stone diagnosis in 28,877 participants in the Mount Sinai BioMe Biobank. In BioMe (1,071 cases and 27,806 controls), for every standard deviation increase, we observed a significant increment in adjusted odds ratio of a factor of 1.2 (95% confidence interval 1.13-1.26). In comparison, a risk score comprised of GWAS significant SNPs was not significantly associated with diagnosis. After stratifying individuals into low and high-risk categories on clinical risk factors, there was a significant increment in adjusted odds ratio of 1.3 (1.12-1.6) in the low- and 1.2 (1.1-1.2) in the high-risk group for every standard deviation increment in PRS. In a 14,348-participant validation cohort (Penn Medicine Biobank), every standard deviation increment was associated with a significant adjusted odds ratio of 1.1 (1.03 - 1.2). Thus, a genome-wide PRS is associated with urinary tract stones overall and in the absence of known clinical risk factors and illustrates their complex polygenic architecture. [Description provided by NIOSH]
• Subjects:
  Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Author Keywords: Genomics Genetic Factors Genomics Heredity Kidney Disorders Kidneys Nephrolithiasis Nephrological Disorders Personalized Medicine Polygenic Risk Score Risk Factors Urinary Tract Stone

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• ISSN:
  0085-2538
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; Florida ; Massachusetts ; New York ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  98
• Issue:
  5
• NIOSHTIC Number:
  nn:20061819
• Citation:
  Kidney Int 2020 Nov; 98(5):1323-1330
• Contact Point Address:
  Girish N. Nadkarni, One Gustave Levy Place, Box 1243, New York, New York 10029, USA
• Email:
  girish.nadkarni@mountsinai.org
• Federal Fiscal Year:
  2021
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  Kidney International
• End Date:
  20200630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:72914e4f6648c7ca9cfa7b9e168fba73b3c70807ec464a1d065abd0d8ef9167a84e5adee43968891c96329259ce1d074c30fc8e01352068fe81f00022a968d11
• Download URL:
  https://stacks.cdc.gov/view/cdc/225192/cdc_225192_DS1.pdf
• File Type:
  [PDF - 687.59 KB ]