ArticleProceedings of the National Academy of Sciences of the United States of America2009
Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 3 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 3 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Effects of NRG1 Polymorphisms on Hirschsprung's Disease Susceptibility: A Meta-analysis.Scientific reports · 2017Pooled it
- Trans-ethnic meta-analysis of genome-wide association studies for Hirschsprung disease.Human molecular genetics · 2016Pooled it
- RET gene is a major risk factor for Hirschsprung's disease: a meta-analysis.Pediatric surgery international · 2015Pooled it
- Combinatorial multiomic analysis from a pedigree of Sox10Dom Hirschsprung mice identifies multiple high confidence candidate modifiers of Enteric Nervous System development.PLoS computational biology · 2026Article
- Zhoushi Qiling decoction inhibits neuregulin 1 secreted from cancer-associated fibroblasts to ameliorate enzalutamide resistance in prostate cancer.Journal of traditional and complementary medicine · 2026Article
- Combinatorial multiomic analysis from a pedigree of Sox10bioRxiv : the preprint server for biology · 2025Article
- EMB is essential for enteric nervous system development mediated by PI3K signaling.Genome medicine · 2025Article
- MicroRNA regulation of enteric nervous system development and disease.Trends in neurosciences · 2025Review
- Neuregulin 1 (NRG1) and its receptors in the enteric nervous system and other parts of the gastrointestinal wall.Histology and histopathology · 2024Review
- Discovery of NRG1-VII: the myeloid-derived class of NRG1.BMC genomics · 2024Article
- RET enhancer haplotype-dependent remodeling of the human fetal gut development program.PLoS genetics · 2023Article
- mRNA sequencing provides new insights into the pathogenesis of Hirschsprung's disease in mice.Pediatric surgery international · 2023Article
- Pathogenic roles of microRNAs and competing endogenous RNAs in Hirschsprung disease (HSCR): Potential diagnostic markers for HSCR.Pediatric discovery · 2023Review
- Combined GWAS and single cell transcriptomics uncover the underlying genes and cell types in disorders of gut-brain interaction.medRxiv : the preprint server for health sciences · 2023Article
- Transcriptomics of Hirschsprung disease patient-derived enteric neural crest cells reveals a role for oxidative phosphorylation.Nature communications · 2023Article
- Genetics of Hirschsprung's disease.Pediatric surgery international · 2023Review
- The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung's disease.Frontiers in cell and developmental biology · 2023Article
- Whole genome sequencing reveals epistasis effects within RET for Hirschsprung disease.Scientific reports · 2022Article
- Review
- The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease.BMC pediatrics · 2022Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 4 countries.
Funding
Abstract
Hirschsprung's disease (HSCR), or aganglionic megacolon, is a congenital disorder characterized by the absence of enteric ganglia in variable portions of the distal intestine. RET is a well-established susceptibility locus, although existing evidence strongly suggests additional loci contributing to sporadic HSCR. To identify these additional genetic loci, we carried out a genome-wide association study using the Affymetrix 500K marker set. We successfully genotyped 293,836 SNPs in 181 Chinese subjects with sporadic HSCR and 346 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Aside from SNPs in RET, the strongest overall associations in plausible candidate genes were found for 2 SNPs located in intron 1 of the neuregulin1 gene (NRG1) on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI(95%):(1.40, 2.00), P = 1.80 x 10(-8)] and 1.98 [CI(95%):(1.59, 2.47), P = 1.12 x 10(-9)], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (P = 0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotype (TT) in the presence of the NRG1 rs7835688 heterozygote, indicating that NRG1 is a modifier of HSRC penetrance. Our highly significant association findings are backed-up by the important role of NRG1 as regulator of the development of the enteric ganglia precursors. The identification of NRG1 as an additional HSCR susceptibility locus not only opens unique fields of investigation into the mechanisms underlying the HSCR pathology, but also the mechanisms by which a discrete number of loci interact with each other to cause disease.
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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.