Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms

Ashish Kapoor, Qian Jiang, Sumantra Chatterjee, Prakash Chakraborty, Maria X. Sosa, Courtney Berrios, Aravinda Chakravarti

Research output: Contribution to journalArticle

Abstract

The risk of Hirschsprung disease (HSCR) is ¡«15/100 000 live births per newborn but has been reported to show significant interindividual variation from the effects of seven common susceptibility alleles at the RET, SEMA3 and NRG1 loci. We show, by analyses of these variants in 997 samples from 376 HSCR families of European ancestry, that significant genetic risk can only be detected at RET (rs2435357 and rs2506030) and at SEMA3 (rs11766001), but not at NRG1. RET rs2435357 also showed significant frequency differences by gender, segment length of aganglionosis and familiality. Further, in combination, disease risk varied >30-fold between individuals with none and up to 6 susceptibility alleles. Thus, these polymorphisms can be used to stratify the newborn population into distinct phenotypic classes with defined risks to understand HSCR etiology.

Original languageEnglish (US)
Article numberddv051
Pages (from-to)2997-3003
Number of pages7
JournalHuman molecular genetics
Volume24
Issue number10
DOIs
StatePublished - May 15 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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