A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
Creators: name: Mingardo, Enrico
name: Beaman, Glenda
name: Grote, Philip
name: Nordenskjöld, Agneta
name: Newman, William
name: Woolf, Adrian S.
name: Eckstein, Markus
name: Hilger, Alina C.
name: Dworschak, Gabriel C.
name: Rösch, Wolfgang
name: Ebert, Anne-Karolin
name: Stein, Raimund
name: Brusco, Alfredo
name: Di Grazia, Massimo
name: Tamer, Ali
name: Torres, Federico M.
name: Hernandez, Jose L.
name: Erben, Philipp
name: Maj, Carlo
name: Olmos, Jose M.
name: Riancho, Jose A.
name: Valero, Carmen
name: Hostettler, Isabel C.
name: Houlden, Henry
name: Werring, David J.
name: Schumacher, Johannes
name: Gehlen, Jan
name: Giel, Ann-Sophie
name: Buerfent, Benedikt C.
name: Arkani, Samara
name: Åkesson, Elisabeth
name: Rotstein, Emilia
name: Ludwig, Michael
name: Holmdahl, Gundela
name: Giorgio, Elisa
name: Berettini, Alfredo
name: Keene, David
name: Cervellione, Raimondo M.
name: Younsi, Nina
name: Ortlieb, Melissa
name: Oswald, Josef
name: Haid, Bernhard
name: Promm, Martin
name: Neissner, Claudia
name: Hirsch, Karin
name: Stehr, Maximilian
name: Schäfer, Frank-Mattias
name: Schmiedeke, Eberhard
name: Boemers, Thomas M.
name: Van Rooij, Iris A. L. M.
name: Feitz, Wouter F. J.
name: Marcelis, Carlo L. M.
name: Lacher, Martin
name: Nelson, Jana
name: Ure, Benno
name: Fortmann, Caroline
name: Gale, Daniel P.
name: Chan, Melanie M. Y.
name: Ludwig, Kerstin U.
name: Nöthen, Markus M.
name: Heilmann, Stefanie
name: Zwink, Nadine
name: Jenetzky, Ekkehart
name: Odermatt, Benjamin
name: Knapp, Michael
name: Reutter, Heiko
Publisher: name: Universität Ulm
Year: 2022
Subjects: Biological Sciences

description: Abstract 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. © In Copyright http://rightsstatements.org/vocab/InC/1.0/
description: A genome-wide association study on classic bladder exstrophy reveals eight genome-wide significant loci, most of which contained genes expressed in embryonic developmental bladder stages. © In Copyright http://rightsstatements.org/vocab/InC/1.0/