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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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. / Reutter, Heiko; Draaken, Markus; Pennimpede, Tracie; Wittler, Lars; Brockschmidt, Felix F; Ebert, Anne-Karolin; Bartels, Enrika; Rösch, Wolfgang; Boemers, Thomas M; Hirsch, Karin; Schmiedeke, Eberhard; Meesters, Christian; Becker, Tim; Stein, Raimund; Utsch, Boris; Mangold, Elisabeth; Nordenskjöld, Agneta; Barker, Gillian; Clementson Kockum, Christina; Zwink, Nadine; Holmdahl, Gundula; Läckgren, Göran; Jenetzky, Ekkehart; Feitz, Wouter Fj; Marcelis, Carlo; Wijers, Charlotte H W; van Rooij, Iris A L M; Gearhart, John P; Herrmann, Bernhard G; Ludwig, Michael; Boyadjiev, Simeon A; Nöthen, Markus M; Mattheisen, Manuel.

In: Human Molecular Genetics, Vol. 23, No. 20, 2014, p. 5536-5544.

Research output: Contribution to journalArticle

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Reutter, H, Draaken, M, Pennimpede, T, Wittler, L, Brockschmidt, FF, Ebert, A-K, Bartels, E, Rösch, W, Boemers, TM, Hirsch, K, Schmiedeke, E, Meesters, C, Becker, T, Stein, R, Utsch, B, Mangold, E, Nordenskjöld, A, Barker, G, Clementson Kockum, C, Zwink, N, Holmdahl, G, Läckgren, G, Jenetzky, E, Feitz, WF, Marcelis, C, Wijers, CHW, van Rooij, IALM, Gearhart, JP, Herrmann, BG, Ludwig, M, Boyadjiev, SA, Nöthen, MM & Mattheisen, M 2014, '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.', Human Molecular Genetics, vol. 23, no. 20, pp. 5536-5544. https://doi.org/10.1093/hmg/ddu259

APA

CBE

Reutter H, Draaken M, Pennimpede T, Wittler L, Brockschmidt FF, Ebert A-K, Bartels E, Rösch W, Boemers TM, Hirsch K, Schmiedeke E, Meesters C, Becker T, Stein R, Utsch B, Mangold E, Nordenskjöld A, Barker G, Clementson Kockum C, Zwink N, Holmdahl G, Läckgren G, Jenetzky E, Feitz WF, Marcelis C, Wijers CHW, van Rooij IALM, Gearhart JP, Herrmann BG, Ludwig M, Boyadjiev SA, Nöthen MM, Mattheisen M. 2014. 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. Human Molecular Genetics. 23(20):5536-5544. https://doi.org/10.1093/hmg/ddu259

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Reutter, Heiko ; Draaken, Markus ; Pennimpede, Tracie ; Wittler, Lars ; Brockschmidt, Felix F ; Ebert, Anne-Karolin ; Bartels, Enrika ; Rösch, Wolfgang ; Boemers, Thomas M ; Hirsch, Karin ; Schmiedeke, Eberhard ; Meesters, Christian ; Becker, Tim ; Stein, Raimund ; Utsch, Boris ; Mangold, Elisabeth ; Nordenskjöld, Agneta ; Barker, Gillian ; Clementson Kockum, Christina ; Zwink, Nadine ; Holmdahl, Gundula ; Läckgren, Göran ; Jenetzky, Ekkehart ; Feitz, Wouter Fj ; Marcelis, Carlo ; Wijers, Charlotte H W ; van Rooij, Iris A L M ; Gearhart, John P ; Herrmann, Bernhard G ; Ludwig, Michael ; Boyadjiev, Simeon A ; Nöthen, Markus M ; Mattheisen, Manuel. / 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. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 20. pp. 5536-5544.

RIS

TY - JOUR

T1 - 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.

AU - Reutter, Heiko

AU - Draaken, Markus

AU - Pennimpede, Tracie

AU - Wittler, Lars

AU - Brockschmidt, Felix F

AU - Ebert, Anne-Karolin

AU - Bartels, Enrika

AU - Rösch, Wolfgang

AU - Boemers, Thomas M

AU - Hirsch, Karin

AU - Schmiedeke, Eberhard

AU - Meesters, Christian

AU - Becker, Tim

AU - Stein, Raimund

AU - Utsch, Boris

AU - Mangold, Elisabeth

AU - Nordenskjöld, Agneta

AU - Barker, Gillian

AU - Clementson Kockum, Christina

AU - Zwink, Nadine

AU - Holmdahl, Gundula

AU - Läckgren, Göran

AU - Jenetzky, Ekkehart

AU - Feitz, Wouter Fj

AU - Marcelis, Carlo

AU - Wijers, Charlotte H W

AU - van Rooij, Iris A L M

AU - Gearhart, John P

AU - Herrmann, Bernhard G

AU - Ludwig, Michael

AU - Boyadjiev, Simeon A

AU - Nöthen, Markus M

AU - Mattheisen, Manuel

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddu259

DO - 10.1093/hmg/ddu259

M3 - Article

VL - 23

SP - 5536

EP - 5544

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 20

ER -