Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 73,475 bioRxiv papers from 319,779 authors.

Distinct Blood DNA Methylation Profiles In Subtypes Of Orofacial Cleft

By Gemma Sharp, Karen Ho, Amy Davies, Evie Stergiakouli, Kerry Humphries, Wendy McArdie, Jonathan Sandy, George Davey Smith, Sarah Lewis, Caroline L Relton

Posted 13 Mar 2017
bioRxiv DOI: 10.1101/113266 (published DOI: 10.1186/s13148-017-0362-2)

Background: There is evidence that different subtypes of orofacial cleft have distinct aetiologies, although the precise molecular mechanisms underlying these are unknown. Given the key role of epigenetic processes such as DNA methylation in embryonic development, it is likely that aberrant DNA methylation may also play a part in the development of orofacial clefts. Methods: In this study, we explored whether blood samples from children with different cleft subtypes showed distinct DNA methylation profiles. In whole blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome. We then carried out epigenome-wide association studies (EWAS) to test the association between methylation at each site and cleft subtype (cleft lip only CLO n=50; cleft palate only CPO n=50; cleft lip and palate CLP n=50). Results: We found four genomic regions differentially methylated in CLO compared to CLP, 17 in CPO compared to CLP and 294 in CPO compared to CLO. These regions included several mapping to genes that have previously been implicated in the development of orofacial clefts (for example, TBX1, COL11A2, HOXA2, PDGFRA) and over 250 novel associations. Conclusion: Our finding of distinct methylation profiles in different cleft subtypes might reflect differences in their aetiologies, with DNA methylation either playing a causal role in development of OFC subtypes or reflecting causal genetic or environmental factors. Key words: Cleft Collective, DNA methylation, epigenome-wide association study, EWAS, cleft lip, cleft palate, orofacial clefts

Download data

  • Downloaded 567 times
  • Download rankings, all-time:
    • Site-wide: 20,356 out of 73,481
    • In epidemiology: 251 out of 1,556
  • Year to date:
    • Site-wide: 37,323 out of 73,481
  • Since beginning of last month:
    • Site-wide: 37,323 out of 73,481

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)