SynthesisPLoS genetics2015
Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy.
Synthesis in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Distinct genetic variants from the whole-exome sequencing of syndromic anorectal malformations: A cross-sectional study.iScience · 2026Article
- Bladder exstrophy on YouTube: an evaluation of quality, actionability, and user engagement.World journal of urology · 2026Article
- Genetic analysis of two bladder exstrophy populations of South Asian and North American origin.Journal of pediatric urology · 2025Article
- Pathophysiology of Congenital Anomalies of the Kidney and Urinary Tract: A Comprehensive Review.Cells · 2024Review
- EZH2 specifically regulates ISL1 during embryonic urinary tract formation.Scientific reports · 2024Article
- Bladder exstrophy-epispadias-cloacal exstrophy complex: characteristics, aetiologies, and epidemiologic findings.African urology · 2024Article
- Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy.American journal of medical genetics. Part A · 2023Article
- The clinical value of prenatal ultrasound in the diagnosis of caudal regression syndrome.American journal of translational research · 2023Article
- A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.Communications biology · 2022Article
- Multidisciplinary approaches for elucidating genetics and molecular pathogenesis of urinary tract malformations.Kidney international · 2022Review
- Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.American journal of medical genetics. Part A · 2021Article
- Review
- Linking glycemic dysregulation in diabetes to symptoms, comorbidities, and genetics through EHR data mining.eLife · 2019Article
- LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh.Cell death & disease · 2019Article
- Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene.Molecular genetics & genomic medicine · 2019Article
- Towards a Central Role ofGenes · 2018Article
- Genetic basis of human congenital anomalies of the kidney and urinary tract.The Journal of clinical investigation · 2018Review
- Evaluation of theHuman genome variation · 2018Article
- Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a.Human molecular genetics · 2018Article
- Role of the LF-SINE-Derived DistalJournal of pediatric genetics · 2017Article
Corrections and comments
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Authors and funding
21 authors at 12 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.