RET and Hirschsprung disease: It is well known that genetic factors play an essential role in the development of HSCR, with RET as the major risk gene, as genome-wide association studies (GWASs) using single nucleotide polymorphism (SNP) chip revealed that RET, SEMA3, and NRG1 were associated with HSCR, which was also confirmed in subsequent independent studies (Garcia-Barcelo et al., 2009; Kim et al., 2014; Jiang et al., 2015; Fadista et al., 2018).