Integrative approaches generate insights into the architecture of non-syndromic cleft lip with or without cleft palate

Julia Welzenbach, Nigel L. Hammond, Miloš Nikolić, Frederic Thieme, Nina Ishorst, Elizabeth J. Leslie, Seth M. Weinberg, Terri H. Beaty, Mary L. Marazita, Elisabeth Mangold, Michael Knapp, Justin Cotney, Alvaro Rada-Iglesias, Michael J. Dixon, Kerstin U. Ludwig

Research output: Contribution to journalArticlepeer-review


Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common congenital facial malformation with a multifactorial etiology. Genome-wide association studies (GWASs) have identified multiple genetic risk loci. However, functional interpretation of these loci is hampered by the underrepresentation in public resources of systematic functional maps representative of human embryonic facial development. To generate novel insights into the etiology of nsCL/P, we leveraged published GWAS data on nsCL/P as well as available chromatin modification and expression data on mid-facial development. Our analyses identified five novel risk loci, prioritized candidate target genes within associated regions, and highlighted distinct pathways. Furthermore, the results suggest the presence of distinct regulatory effects of nsCL/P risk variants throughout mid-facial development and shed light on its regulatory architecture. Our integrated data provide a platform to advance hypothesis-driven molecular investigations of nsCL/P and other human facial defects.

Original languageEnglish (US)
Article number100038
JournalHuman Genetics and Genomics Advances
Issue number3
StatePublished - Jul 8 2021


  • GWAS
  • chromatin mark
  • cleft
  • craniofacial development
  • regulatory effects

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics(clinical)


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