6533b859fe1ef96bd12b80ee
RESEARCH PRODUCT
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
Simeon A. BoyadjievJohn P. GearhartGundula HolmdahlCharlotte H. W. WijersRaimund SteinThomas M. BoemersMarkus M. NöthenChristian MeestersKarin HirschTracie PennimpedeWolfgang RöschNadine ZwinkEnrika BartelsTim BeckerTim BeckerCarlo MarcelisMarkus DraakenWouter F.j. FeitzManuel MattheisenManuel MattheisenManuel MattheisenBernhard G. HerrmannAgneta NordenskjöldAgneta NordenskjöldAnne K. EbertGöran LäckgrenHeiko ReutterEberhard SchmiedekeEkkehart JenetzkyEkkehart JenetzkyIris A.l.m. Van RooijElisabeth MangoldChristina Clementson KockumLars WittlerMichael LudwigFelix F. BrockschmidtBoris UtschGillian Barkersubject
genetics [Wnt3 Protein]Genome-wide association studyGenomeConserved sequenceMiceIntergenic regionMedizinische FakultätSALL1 protein humanGenetics (clinical)Conserved SequenceGeneticsgenetics [Wnt Proteins]Association Studies ArticlesGeneral Medicinegenetics [Transcription Factors]genetics [European Continental Ancestry Group]WNT3 protein humanReconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]metabolism [Wnt3 Protein]Medical geneticsmedicine.medical_specialtygenetics [White People]WNT9B protein human-BiologyPolymorphism Single NucleotideWhite Peopleembryology [Genitalia]Wnt3 Proteinpathology [Bladder Exstrophy]metabolism [Wnt Proteins]genetics [Bladder Exstrophy]ddc:570GeneticsmedicineAnimalsHumansGenetic Predisposition to Diseaseddc:610GenitaliaMolecular BiologyGeneBase SequenceBladder ExstrophyCase-control studymedicine.diseasemetabolism [Genitalia]Bladder exstrophyWnt ProteinsReconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10]Case-Control StudiesGenome-Wide Association StudyTranscription Factorsdescription
Item does not contain fulltext 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-05-22 |