Although functional evaluation is required, we supply new evidence for the NRG1 to HSCR and raised up a new susceptibility gene AUTS2 to a specific symptom for the disease.
The incidence of HSCR is approximately 1 of 5000 live births; however, the risk shows remarkable individual variation caused by single nucleotide polymorphisms (SNPs) at the RET, SEMA3, and NRG1 loci.
The risk of Hirschsprung disease (HSCR) is ∼15/100 000 live births per newborn but has been reported to show significant inter-individual variation from the effects of seven common susceptibility alleles at the RET, SEMA3 and NRG1 loci.
Although RET is a well-established risk factor, a recent genome-wide association study (GWAS) of HSCR has identified NRG1 as an additional susceptibility locus.
To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus.
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.