AUTHOR=van der Zanden Loes F. M. , Maj Carlo , Borisov Oleg , van Rooij Iris A. L. M. , Quaedackers Josine S. L. T. , Steffens Martijn , Schierbaum Luca , Schneider Sophia , Waffenschmidt Lea , Kiemeney Lambertus A. L. M. , de Wall Liesbeth L. L. , Heilmann Stefanie , Hofmann Aybike , Gehlen Jan , Schumacher Johannes , Szczepanska Maria , Taranta-Janusz Katarzyna , Kroll Pawel , Krzemien Grazyna , Szmigielska Agnieszka , Schreuder Michiel F. , Weber Stefanie , Zaniew Marcin , Roeleveld Nel , Reutter Heiko , Feitz Wout F. J. , Hilger Alina C. TITLE=Genome-wide association study in patients with posterior urethral valves JOURNAL=Frontiers in Pediatrics VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.988374 DOI=10.3389/fped.2022.988374 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.