Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy

PLoS Genetics
Markus DraakenHeiko Reutter

Abstract

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10-12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, ...Continue Reading

References

Feb 1, 1988·Journal of Pediatric Surgery·H MildenbergerM Dziuba
Aug 1, 1984·The Journal of Urology·E ShapiroR D Jeffs
Jun 1, 1994·Journal of Medical Genetics·E J MesselinkA Vos
May 10, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yunhua Li MullerClaudia Kappen
Jul 2, 2003·American Journal of Medical Genetics. Part a·Heiko ReutterJeffrey R Gruen
May 12, 2006·Developmental Biology·Lizhu LinSylvia Evans
Oct 17, 2007·American Journal of Medical Genetics. Part a·Heiko ReutterSimeon A Boyadjiev
Jan 24, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Michael LudwigSimeon A Boyadjiev
Nov 3, 2009·Orphanet Journal of Rare Diseases·Anne-Karoline EbertWolfgang H Rösch
Jan 5, 2010·European Journal of Medical Genetics·Johanna LundinAgneta Nordenskjöld
Jan 12, 2010·European Journal of Medical Genetics·Markus DraakenMichael Ludwig
Oct 12, 2010·Bioinformatics·Ani ManichaikulWei-Min Chen
May 4, 2013·Journal of the American Society of Nephrology : JASN·Yusuke KakuRyuichi Nishinakamura
May 9, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·K AnamT A Davis
Jun 15, 2013·Developmental Cell·Arnon Dias JurbergMoisés Mallo
Aug 3, 2013·Gene Expression Patterns : GEP·Shaowei ZhuangYunfu Sun
Aug 6, 2013·Birth Defects Research. Part A, Clinical and Molecular Teratology·Lihong QiSimeon A Boyadjiev
Apr 26, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Markus DraakenHeiko Reutter

❮ Previous
Next ❯

Citations

Jun 25, 2015·Human Molecular Genetics·Izabella Baranowska KörbergAgneta Nordenskjöld
Dec 6, 2016·International Neurourology Journal·Akihiro Kanematsu
Sep 30, 2017·American Journal of Medical Genetics. Part a·Kim M Keppler-NoreuilUNKNOWN National Birth Defects Prevention Study
Apr 6, 2018·Human Genome Variation·Samara ArkaniAgneta Nordenskjöld
May 4, 2016·BMC Medical Genetics·Catharina von LowtzowMarkus Draaken
Jan 3, 2018·The Journal of Clinical Investigation·Simone Sanna-CherchiAli G Gharavi
Oct 14, 2020·Urology·Saran A HallJohn P Gearhart
Nov 3, 2020·Journal of Pediatric Orthopedics·Ethan CottrillPaul D Sponseller
Aug 7, 2021·American Journal of Medical Genetics. Part a·Georgia PitsavaUNKNOWN University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program and the National Birth Defects P
Aug 28, 2021·Genes·Glenda M BeamanWilliam G Newman

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
Assay
MDS

Software Mentioned

MutPred
Ensembl
SNPs
ENCODE
KING
SIFT
Go
IMPUTE2
TFSEARCH

Related Concepts

Related Feeds

Bladder Carcinoma In Situ

Bladder Carcinoma In Situ is a superficial bladder cancer that occurs on the surface layer of the bladder. Discover the latest research on this precancerous condition in this feed.