title: Contribution of Common Variants in GABRG2, RELN and NRG3 and Interaction Networks to the Risk of Hirschsprung Disease.
abstract: BACKGROUND
  Hirschsprung disease (HSCR) is a complex and heterogeneous disorder, characterized by a deficit in enteric nervous system. Genome-wide studies implied GABRG2, RELN and NRG3 might be involved in HSCR etiology. Here, we aimed to assess genetic variants in GABRG2, RELN and NRG3 that may confer susceptibility to HSCR and explore genetic interaction networks in HSCR.
  
  
  METHODS
  Using a strategy that combined case-control study and gene-gene interaction analysis with the MassArray system, we evaluated 24 polymorphisms within GABRG2, RELN and NRG3 in 104 HSCR cases and 151 normal controls of Han Chinese origin.
  
  
  RESULTS
  We observed that seven polymorphisms showed statistically significant differences between HSCR subjects and normal controls. For each of the three genes, the haplotypes which combined eight markers were the most significant. Moreover, we recruited SNPsyn, GO enrichment and MDR analyses to interrogate the interactions among GABRG2, RELN, NRG3 and our previous identified PTCH1 gene. Significant interaction networks were found among GABRG2, RELN, and PTCH1.
  
  
  CONCLUSIONS
  We provide a first indication that common variants of GABRG2, RELN and NRG3 and the GABRG2-RELN-PTCH1 interaction networks might confer altered susceptibility to HSCR in the Han Chinese population, suggesting a potential mechanism underlying HSCR pathogenesis.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wei
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.forename: Junkai
authors.initials: J
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D013058:Mass Spectrometry; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020880:Neuregulins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D000091042:Reelin Protein; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; C546279:GABRG2 protein, human; C486357:NRG3 protein, human; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D011963:Receptors, GABA-A; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases