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.
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.
Funder
Nierstichting
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Deutsche Forschungsgemeinschaft
Else Kröner-Fresenius-Stiftung
Eva Luise und Horst Köhler Stiftung
Subject
Pediatrics, Perinatology and Child Health
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献