Genome-wide association study and mouse expression data identify a highly conserved 32kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.

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Bibtex

@article{8e66e8e48c504a44b94ac814df4755de,
title = "Genome-wide association study and mouse expression data identify a highly conserved 32kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.",
abstract = "Bladder Exstrophy-Epispadias Complex (BEEC), the severe end of the uro-rectal 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 218/865 cases/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 32kb 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.",
author = "Heiko Reutter and Markus Draaken and Tracie Pennimpede and Lars Wittler and Brockschmidt, {Felix F} and Anne-Karolin Ebert and Enrika Bartels and Wolfgang R{\"o}sch and Boemers, {Thomas M} and Karin Hirsch and Eberhard Schmiedeke and Christian Meesters and Tim Becker and Raimund Stein and Boris Utsch and Elisabeth Mangold and Agneta Nordenskj{\"o}ld and Gillian Barker and {Clementson Kockum}, Christina and Nadine Zwink and Gundula Holmdahl and G{\"o}ran L{\"a}ckgren and Ekkehart Jenetzky and Feitz, {Wouter Fj} and Carlo Marcelis and Wijers, {Charlotte H W} and {van Rooij}, {Iris A L M} and Gearhart, {John P} and Herrmann, {Bernhard G} and Michael Ludwig and Boyadjiev, {Simeon A} and N{\"o}then, {Markus M} and Manuel Mattheisen",
year = "2014",
doi = "10.1093/hmg/ddu259",
language = "English",
volume = "23",
pages = "5536--5544",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "20",

}