Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease

TitleGenome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease
Authors
Issue Date2009
PublisherWiley-Blackwell. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1350-1925&site=1
Citation
The Second International Symposium on Development of the Enteric Nervous System: Cells, Signals and Genes, London, 22-25 February 2009. In Neurogastroenterology & Motility, 2009, v. 21 n.2, p. XXVII How to Cite?
Abstract
Background and objectives: 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. Methods: We genotyped 4 93 840 single-nucleotide polymorphisms (SNPs) in 200 Chinese subjects with sporadic HSCR and 306 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Results: Aside from SNPs in RET, the strongest overall associations were found for two 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 · 10–8] and 1.98 [CI 95%:(1.59, 2.47), P = 1.12 · 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. Conclusions: 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 a new HSCR susceptibility locus not only opens new 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.
Persistent Identifierhttp://hdl.handle.net/10722/143705
ISSN
2013 Impact Factor: 3.424
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTam, PKHen_US
dc.contributor.authorTang, CSMen_US
dc.contributor.authorNgan, ESWen_US
dc.contributor.authorLui, VCHen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorSo, MTen_US
dc.contributor.authorLeon, TYYen_US
dc.contributor.authorMiao, XPen_US
dc.contributor.authorShum, CKYen_US
dc.contributor.authorLiu, FQen_US
dc.contributor.authorYeung, MYen_US
dc.contributor.authorYuan, ZWen_US
dc.contributor.authorGuo, WHen_US
dc.contributor.authorLiu, Len_US
dc.contributor.authorSun, XBen_US
dc.contributor.authorHuang, LMen_US
dc.contributor.authorTou, JFen_US
dc.contributor.authorSong, YQen_US
dc.contributor.authorChan, Den_US
dc.contributor.authorCheung, KMCen_US
dc.contributor.authorWong, KKYen_US
dc.contributor.authorCherny, SSen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorGarcia-Barcelo, MMen_US
dc.date.accessioned2011-12-16T08:09:51Z-
dc.date.available2011-12-16T08:09:51Z-
dc.date.issued2009en_US
dc.identifier.citationThe Second International Symposium on Development of the Enteric Nervous System: Cells, Signals and Genes, London, 22-25 February 2009. In Neurogastroenterology & Motility, 2009, v. 21 n.2, p. XXVIIen_US
dc.identifier.issn1350-1925en_US
dc.identifier.urihttp://hdl.handle.net/10722/143705-
dc.description.abstractBackground and objectives: 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. Methods: We genotyped 4 93 840 single-nucleotide polymorphisms (SNPs) in 200 Chinese subjects with sporadic HSCR and 306 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Results: Aside from SNPs in RET, the strongest overall associations were found for two 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 · 10–8] and 1.98 [CI 95%:(1.59, 2.47), P = 1.12 · 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. Conclusions: 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 a new HSCR susceptibility locus not only opens new 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.-
dc.publisherWiley-Blackwell. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1350-1925&site=1en_US
dc.relation.ispartofNEUROGASTROENTEROLOGY AND MOTILITYen_US
dc.titleGenome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's diseaseen_US
dc.typeConference_Paperen_US
dc.identifier.emailCherny, SS: cherny@hku.hken_US
dc.identifier.authorityCherny, SS=rp00232en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1365-2982.2008.01253.x-
dc.identifier.volume21en_US
dc.identifier.spageXXVIIen_US
dc.identifier.epageXXVIIen_US
dc.identifier.isiWOS:000262688300109-
dc.description.otherThe Second International Symposium on Development of the Enteric Nervous System: Cells, Signals and Genes, London, 22-25 February 2009. In Neurogastroenterology & Motility, 2009, v. 21 n.2, p. XXVII-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats