Genome-wide association study in patients with posterior urethral valves

van der Zanden LF, Maj C, Borisov O, van Rooij IA, Quaedackers JS, Steffens M, Schierbaum L, Schneider S, Waffenschmidt L, Kiemeney LA, de Wall LL, Heilmann S, Hofmann A, Gehlen J, Schumacher J, Szczepanska M, Taranta-Janusz K, Kroll P, Krzemien G, Szmigielska A, Schreuder MF, Weber S, Zaniew M, Roeleveld N, Reutter HM, Feitz WF, Hilger AC (2022)

Publication Type: Journal article

Publication year: 2022


Book Volume: 10

Article Number: 988374

DOI: 10.3389/fped.2022.988374


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.

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van der Zanden, L.F., Maj, C., Borisov, O., van Rooij, I.A., Quaedackers, J.S., Steffens, M.,... Hilger, A.C. (2022). Genome-wide association study in patients with posterior urethral valves. Frontiers in Pediatrics, 10.


van der Zanden, Loes F.M., et al. "Genome-wide association study in patients with posterior urethral valves." Frontiers in Pediatrics 10 (2022).

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