A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy

Enrico Mingardo; Glenda Beaman; Philip Grote; Agneta Nordenskjöld; William Newman; Adrian S. Woolf; Markus Eckstein; Alina C. Hilger; Gabriel C. Dworschak; Wolfgang Rösch; Anne-Karolin Ebert; Raimund Stein; Alfredo Brusco; Massimo Di Grazia; Ali Tamer; Federico M. Torres; Jose L. Hernandez; Philipp Erben; Carlo Maj; Jose M. Olmos; Jose A. Riancho; Carmen Valero; Isabel C. Hostettler; Henry Houlden; David J. Werring; Johannes Schumacher; Jan Gehlen; Ann-Sophie Giel; Benedikt C. Buerfent; Samara Arkani

AutorIn: Enrico Mingardo; Glenda Beaman; Philip Grote; Agneta Nordenskjöld; William Newman; Adrian S. Woolf; Markus Eckstein; Alina C. Hilger; Gabriel C. Dworschak; Wolfgang Rösch; Anne-Karolin Ebert; Raimund Stein; Alfredo Brusco; Massimo Di Grazia; Ali Tamer; Federico M. Torres; Jose L. Hernandez; Philipp Erben; Carlo Maj; Jose M. Olmos; Jose A. Riancho; Carmen Valero; Isabel C. Hostettler; Henry Houlden; David J. Werring; Johannes Schumacher; Jan Gehlen; Ann-Sophie Giel; Benedikt C. Buerfent; Samara Arkani
Titel: A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
Zitierfähige Url:: https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-1035283
Quellenangabe: Communications Biology
Erscheinungsjahr: 2022

Jahrgang: 5
Heft: 1
E-ISSN: 2399-3642
Artikelnummer: 1203
Erstveröffentlichung: 2022
Abstract (EN): Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
Andere Ausgabe: Erstveröffentlichung
DOI: 10.1038/s42003-022-04092-3
Freie Schlagwörter (EN): classic bladder exstrophy, genetic drivers, genome-wide association study
Klassifikation (DDC): 570
Verlag: Nature Publishing Group UK, London
Version / Begutachtungsstatus: publizierte Version / Verlagsversion
URN Qucosa: urn:nbn:de:bsz:15-qucosa2-1035283
Veröffentlichungsdatum Qucosa: 30.03.2026
Dokumenttyp: Artikel
Sprache des Dokumentes: Englisch
Lizenz / Rechtehinweis: CC BY 4.0

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