학술논문
Genome-wide association study in patients with posterior urethral valves
Document Type
article
Author
Loes F. M. van der Zanden; Carlo Maj; Oleg Borisov; Iris A. L. M. van Rooij; Josine S. L. T. Quaedackers; Martijn Steffens; Luca Schierbaum; Sophia Schneider; Lea Waffenschmidt; Lambertus A. L. M. Kiemeney; Liesbeth L. L. de Wall; Stefanie Heilmann; Aybike Hofmann; Jan Gehlen; Johannes Schumacher; Maria Szczepanska; Katarzyna Taranta-Janusz; Pawel Kroll; Grazyna Krzemien; Agnieszka Szmigielska; Michiel F. Schreuder; Stefanie Weber; Marcin Zaniew; Nel Roeleveld; Heiko Reutter; Wout F. J. Feitz; Alina C. Hilger
Source
Frontiers in Pediatrics, Vol 10 (2022)
Subject
Language
English
ISSN
2296-2360
Abstract
Congenital lower urinary tract obstructions (LUTO) are most often caused by posterior urethral valves (PUV), a male limited anatomical obstruction of the urethra affecting 1 in 4,000 male live births. Little is known about the genetic background of PUV. Here, we report the largest genome-wide association study (GWAS) for PUV in 4 cohorts of patients and controls. The final meta-analysis included 756 patients and 4,823 ethnicity matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts. No genome-wide significant locus was identified, but 33 variants showed suggestive significance (P < 1 × 10−5). When considering only loci with multiple variants residing within < 10 kB of each other showing suggestive significance and with the same effect direction in all 4 cohorts, 3 loci comprising a total of 9 variants remained. These loci resided on chromosomes 13, 16, and 20. The present GWAS and meta-analysis is the largest genetic study on PUV performed to date. The fact that no genome-wide significant locus was identified, can be explained by lack of power or may indicate that common variants do not play a major role in the etiology of PUV. Nevertheless, future studies are warranted to replicate and validate the 3 loci that yielded suggestive associations.