Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate

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DOI

  • Laurence J. Howe, Bristol University, University College London
  • ,
  • Tom G. Richardson, Bristol University
  • ,
  • Ryan Arathimos, Bristol University
  • ,
  • Lucas Alvizi, Universidade de São Paulo – USP
  • ,
  • Maria R. Passos-Bueno
  • ,
  • Philip Stanier, University College London
  • ,
  • Ellen Nohr
  • ,
  • Kerstin U. Ludwig, University of Bonn
  • ,
  • Elisabeth Mangold, University of Bonn
  • ,
  • Michael Knapp, University of Bonn
  • ,
  • Evie Stergiakouli, Bristol University
  • ,
  • Beate St Pourcain, Bristol University, Max Planck Institute for Psycholinguistics, Donders Institute for Brain
  • ,
  • George Davey Smith, Bristol University
  • ,
  • Jonathan Sandy, Bristol University
  • ,
  • Caroline L. Relton, Bristol University
  • ,
  • Sarah J. Lewis, Bristol University
  • ,
  • Gibran Hemani, Bristol University
  • ,
  • Gemma C. Sharp, Bristol University

Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.

OriginalsprogEngelsk
TidsskriftEpigenomics
Vol/bind11
Nummer2
Sider (fra-til)133-145
Antal sider13
ISSN1750-1911
DOI
StatusUdgivet - feb. 2019

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