Distinct DNA methylation profiles in subtypes of orofacial cleft

• DOI: 10.1186/s13148-017-0362-2
• Publication Date: 2017-06-08T12:05:48Z
• Authors: Gemma C. Sharp; Karen Ho; Amy Davies; Evie Stergiakouli; Kerry Humphries; Wendy McArdle; Jonathan Sandy; George Davey Smith; Sarah J. Lewis; Caroline L. Relton
• Keywords: Human genetics

Epigenetic data could help identify risk factors for orofacial clefts, either by revealing a causal role epigenetic mechanisms in causing clefts or capturing information about genetic environmental factors. Given the evidence that different subtypes of cleft have distinct aetiologies, we explored whether children with showed profiles.In whole-blood samples from 150 Cleft Collective cohort study, measured DNA methylation at over 450,000 sites on genome. We then carried out epigenome-wide association studies (EWAS) to test between each site and subtype (cleft lip only (CLO) n = 50; palate (CPO) (CLP) 50). also compared blood tissue using genome-wide same conducted an EWAS CLO CLP tissue.We found four genomic regions differentially methylated CLP, 17 CPO 294 CLO. Several mapped genes previously been implicated development (for example, TBX1, COL11A2, HOXA2, PDGFRA), 250 associations were novel. Methylation correlated lip/palate some regions. There 14 one region (near KIAA0415) showing up both EWAS.Our finding profiles (OFC) represents promising first step exploring potential modifications aetiology OFCs and/or as clinically useful biomarkers OFC subtypes.