ESPN 54th Annual Meeting

ESPN 2022


 
Genome-wide association study in patients with anatomical obstructions of the lower urinary tract
LOES F. M. VAN DER ZANDEN 1 CARLO MAJ 2 OLEG BORISOV 2 IRIS A. L. M. VAN ROOIJ 1 JOSINE S.L.T. QUAEDACKERS 3 MARTIJN STEFFENS 4 LUCA SCHIERBAUM 5 SOPHIA SCHNEIDER 5 LEA WAFFENSCHMIDT 5 LAMBERT A.L.M KIEMENEY 1 LIESBETH DE WALL 6 STEFANIE HEILMANN 5 WOLFGANG RÖSCH 7 JAN GEHLEN 8 JOHANNES SCHUMACHER 8 MARIA SZCZEPANSKA 15 KATARZYNA TARANTA-JANUSZ 9 GRAZYNA KRZEMIEN 10 AGNIESZKA SZMIGIELSKA 10 MICHIEL SCHREUDER 11 STEFANIE WEBER 12 MARCIN ZANIEW 13 NEL ROELEVELD 1 HEIKO REUTTER 14 WOUT FEITZ 6 ALINA C. HILGER 16

1- RADBOUD INSTITUTE FOR HEALTH SCIENCES, DEPARTMENT FOR HEALTH EVIDENCE, RADBOUD UNIVERSITY MEDICAL CENTER, NIJMEGEN, THE NETHERLANDS
2- INSTITUTE FOR GENOMIC STATISTICS AND BIOINFORMATICS, MEDICAL FACULTY, UNIVERSITY OF BONN, GERMANY
3- DEPARTMENT OF UROLOGY, UNIVERSITY MEDICAL CENTER GRONINGEN, GRONINGEN, THE NETHERLANDS
4- DEPARTMENT OF UROLOGY, ISALA, ZWOLLE, THE NETHERLANDS
5- INSTITUTE OF HUMAN GENETICS, UNIVERSITY HOSPITAL OF BONN, BONN, GERMANY
6- RADBOUD INSTITUTE FOR MOLECULAR LIFE SCIENCES, DIVISION OF PEDIATRIC UROLOGY, DEPARTMENT OF UROLOGY, RADBOUDUMC AMALIA CHILDREN’S HOSPITAL, NIJMEGEN, THE NETHERLANDS
7- DEPARTMENT OF PEDIATRIC UROLOGY, CLINIC ST. HEDWIG, UNIVERSITY MEDICAL CENTER REGENSBURG, REGENSBURG, GERMANY
8- CENTER FOR HUMAN GENETICS, UNIVERSITY HOSPITAL OF MARBURG, MARBURG, GERMANY
9- DEPARTMENT OF PEDIATRICS AND NEPHROLOGY, MEDICAL UNIVERSITY OF BIAłYSTOK, BIAłYSTOK, POLAND
10- DEPARTMENT OF PEDIATRICS AND NEPHROLOGY, MEDICAL UNIVERSITY OF WARSAW, WARSAW, POLAND.
11- RADBOUD INSTITUTE FOR MOLECULAR LIFE SCIENCES, DEPARTMENT OF PEDIATRIC NEPHROLOGY, RADBOUDUMC AMALIA CHILDREN’S HOSPITAL, NIJMEGEN, THE NETHERLANDS
12- UNIVERSITY CHILDREN HOSPITAL MARBURG, PHILIPPS UNIVERSITY MARBURG, MARBURG, GERMANY.
13- DEPARTMENT OF PEDIATRICS, UNIVERSITY OF ZIELONA GóRA, ZIELONA GóRA, POLAND
14- DIVISION OF NEONATOLOGY AND PEDIATRIC INTENSIVE CARE, DEPARTMENT OF PEDIATRICS AND ADOLESCENT MEDICINE, FRIEDRICH-ALEXANDER UNIVERSITY OF ERLANGEN-NÜRNBERG, ERLANGEN, GERMANY
15- DEPARTMENT OF PEDIATRICS, FACULTY OF MEDICAL SCIENCES IN ZABRZE, MEDICAL UNIVERSITY OF SILESIA IN KATOWICE, ZABRZE, POLAND
16- DEPARTMENT OF PEDIATRICS AND ADOLESCENT MEDICINE, FRIEDRICH-ALEXANDER UNIVERSITY OF ERLANGEN-NÜRNBERG, ERLANGEN, GERMANY
 
Introduction:

Congenital lower urinary tract obstruction (LUTO) is most often caused by an anatomical blockage of the urethra most commonly posterior urethral valves (PUV), a male limited phenotype affecting 1 in 4,000 male live births. Little is known about the genetic background of anatomical LUTO. Here, we report the first study using genome-wide association methods to analyze anatomical LUTO in 4 cohorts of patients and controls.

Material and methods:

The final meta-analysis comprised 758 patients and 4,823 ethnically matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts.

Results:

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 <10kB of each other showing suggestive significance and with same effect direction in all four cohorts, three loci comprising together nine variants remained. Loci resided on chromosome 13, 16 , and 20.

Conclusions:

The present GWAS and meta-analysis is the largest genetic study on anatomical LUTO performed to date. The fact that no genome-wide significant locus could be identified, could be explained by the lack of power or may indicate that common variants do not play a major role in the aetiology of anatomical LUTO. Nevertheless, three loci yielded suggestive association. Future studies are warranted to support these loci.