Frontiers in Pediatrics (Sep 2022)
Genome-wide association study in patients with posterior urethral valves
- 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,
- Alina C. Hilger,
- Alina C. Hilger
Affiliations
- Loes F. M. van der Zanden
- Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Carlo Maj
- Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Bonn, Germany
- Oleg Borisov
- Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Bonn, Germany
- Iris A. L. M. van Rooij
- Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Josine S. L. T. Quaedackers
- Department of Urology, University Medical Center Groningen, Groningen, Netherlands
- Martijn Steffens
- Department of Urology, Isala, Zwolle, Netherlands
- Luca Schierbaum
- Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany
- Sophia Schneider
- Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany
- Lea Waffenschmidt
- Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany
- Lambertus A. L. M. Kiemeney
- Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Liesbeth L. L. de Wall
- Division of Pediatric Urology, Department of Urology, Radboud Institute for Molecular Life Sciences, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
- Stefanie Heilmann
- Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany
- Aybike Hofmann
- Department of Pediatric Urology, Clinic St. Hedwig, University Medical Center Regensburg, Regensburg, Germany
- Jan Gehlen
- Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
- Johannes Schumacher
- Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
- Maria Szczepanska
- Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Zabrze, Poland
- Katarzyna Taranta-Janusz
- 0Department of Pediatrics and Nephrology, Medical University of Białystok, Białystok, Poland
- Pawel Kroll
- 1Neurourology Unit, Pediatric Surgery and Urology Clinic, Poznań, Poland
- Grazyna Krzemien
- 2Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland
- Agnieszka Szmigielska
- 2Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland
- Michiel F. Schreuder
- 3Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
- Stefanie Weber
- 4University Children Hospital Marburg, Philipps University Marburg, Marburg, Germany
- Marcin Zaniew
- 5Department of Pediatrics, University of Zielona Góra, Zielona Góra, Poland
- Nel Roeleveld
- Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Heiko Reutter
- 6Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany
- Wout F. J. Feitz
- Division of Pediatric Urology, Department of Urology, Radboud Institute for Molecular Life Sciences, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
- Alina C. Hilger
- Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany
- Alina C. Hilger
- 7Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany
- Alina C. Hilger
- 8Research Center on Rare Kidney Diseases, University Hospital Erlangen, Erlangen, Germany
- DOI
- https://doi.org/10.3389/fped.2022.988374
- Journal volume & issue
-
Vol. 10
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.
Keywords
- genome wide association study
- lower urinary tract obstruction
- obstructive uropathy
- posterior urethral valves
- PCDH9
- SALL1
