Journal article
Authors list: Reutter, Heiko; Draaken, Markus; Pennimpede, Tracie; Wittler, Lars; Brockschmidt, Felix F.; Ebert, Anne-Karolin; Bartels, Enrika; Roesch, Wolfgang; Boemers, Thomas M.; Hirsch, Karin; Schmiedeke, Eberhard; Meesters, Christian; Becker, Tim; Stein, Raimund; Utsch, Boris; Mangold, Elisabeth; Nordenskjoeld, Agneta; Barker, Gillian; Kockum, Christina Clementsson; Zwink, Nadine; Holmdahl, Gundula; Laeckgren, Goeran; Jenetzky, Ekkehart; Feitz, Wouter F. J.; Marcelis, Carlo; Wijers, Charlotte H. W.; Van Rooij, Iris A. L. M.; Gearhart, John P.; Herrmann, Bernhard G.; Ludwig, Michael; Boyadjiev, Simeon A.; Noethen, Markus M.; Mattheisen, Manuel
Publication year: 2014
Pages: 5536-5544
Journal: Human Molecular Genetics
Volume number: 23
Issue number: 20
ISSN: 0964-6906
eISSN: 1460-2083
Open access status: Green
DOI Link: https://doi.org/10.1093/hmg/ddu259
Publisher: Oxford University Press
Abstract:
Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our discovery sample identified a marker near SALL1, showing genome-wide significant association with CBE. However, analyses performed on follow-up samples did not add further support to these findings. We were also able to identify an association with CBE across our study samples (discovery: P = 8.88 x 10(-5); follow-up: P = 0.0025; combined: 1.09 x 10(-6)) in a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in the genital region during stages relevant to the development of CBE in humans. Unfortunately, we were not able to replicate the suggestive signal for WNT3 and WNT9B in a sample that was enriched for non-CBE BEEC cases (P = 0.51). Our suggestive findings support the hypothesis that larger samples are warranted to identify association of common variation with CBE.
Citation Styles
Harvard Citation style: Reutter, H., Draaken, M., Pennimpede, T., Wittler, L., Brockschmidt, F., Ebert, A., et al. (2014) Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder, Human Molecular Genetics, 23(20), pp. 5536-5544. https://doi.org/10.1093/hmg/ddu259
APA Citation style: Reutter, H., Draaken, M., Pennimpede, T., Wittler, L., Brockschmidt, F., Ebert, A., Bartels, E., Roesch, W., Boemers, T., Hirsch, K., Schmiedeke, E., Meesters, C., Becker, T., Stein, R., Utsch, B., Mangold, E., Nordenskjoeld, A., Barker, G., Kockum, C., ...Mattheisen, M. (2014). Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder. Human Molecular Genetics. 23(20), 5536-5544. https://doi.org/10.1093/hmg/ddu259
Keywords
DYSREGULATION; EPISPADIAS COMPLEX; GUDMAP; imputation; PLAYS; SALL1; TOWNES-BROCKS-SYNDROME
