Evaluation of Genetic Associations with Clinical Phenotypes of Kidney Stone Disease

Bibliographic Details
Title:	Evaluation of Genetic Associations with Clinical Phenotypes of Kidney Stone Disease
Authors:	Ryan S. Hsi, Siwei Zhang, Jefferson L. Triozzi, Adriana M. Hung, Yaomin Xu, Cosmin A. Bejan
Source:	European Urology Open Science, Vol 67, Iss , Pp 38-44 (2024)
Publisher Information:	Elsevier, 2024.
Publication Year:	2024
Collection:	LCC:Diseases of the genitourinary system. Urology LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms:	Kidney calculi, Nephrolithiasis, Precision phenotyping, Electronic health records, Genome-wide association study, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details:	Background and objective: Previous studies have reported a strong genetic contribution to kidney stone risk. This study aims to identify genetic associations of kidney stone disease within a large-scale electronic health record system. Methods: We performed genome-wide association studies (GWASs) for nephrolithiasis from genotyped samples of 5571 cases and 83 692 controls. This analysis included a primary GWAS focused on nephrolithiasis and subsequent subgroup GWASs stratified by stone composition types. For significant risk variants, we performed association analyses with stone composition and first-time 24-h urine parameters. To assess disease severity, we investigated the associations with age at first stone diagnosis, age at first stone-related procedure, and time between first and second stone-related procedures. Key findings and limitations: The primary GWAS analysis identified ten significant loci, all located on chromosome 16 within coding regions of the UMOD gene. The strongest signal was rs28544423 (odds ratio 1.17, 95% confidence interval 1.11–1.23, p = 2.7 × 10–9). In subgroup GWASs stratified by six kidney stone composition subtypes, 19 significant loci were identified including two loci in coding regions (brushite; NXPH1, rs79970906 and rs4725104). The UMOD single nucleotide polymorphism rs28544423 was associated with differences in 24-h excretion of urinary analytes, and the minor allele was positively associated with calcium oxalate dihydrate stone composition (p
Document Type:	article
File Description:	electronic resource
Language:	English
ISSN:	2666-1683
Relation:	http://www.sciencedirect.com/science/article/pii/S2666168324006037; https://doaj.org/toc/2666-1683
DOI:	10.1016/j.euros.2024.07.109
Access URL:	https://doaj.org/article/d5dfc959fee140d3b943dcfcbd703365
Accession Number:	edsdoj.5dfc959fee140d3b943dcfcbd703365
Database:	Directory of Open Access Journals

More Details
ISSN:	26661683
DOI:	10.1016/j.euros.2024.07.109
Published in:	European Urology Open Science
Language:	English