In conclusion, this study demonstrates that common genetic variants, rs2439302 (NRG1) GG increase the risk of developing HSCR by affecting the binding of transcription factor CTCF and interacting with rs2435357 (RET) via SOX10/PI3K/Akt pathway and provided further evidence in the relationship of NRG1 abnormal expression with HSCR pathogenesis. This evidence concerns the gene RET and Hirschsprung disease.