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

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...

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Detalles Bibliográficos
Autores principales: Howe, Laurence J, Richardson, Tom G, Arathimos, Ryan, Alvizi, Lucas, Passos-Bueno, Maria R, Stanier, Philip, Nohr, Ellen, Ludwig, Kerstin U, Mangold, Elisabeth, Knapp, Michael, Stergiakouli, Evie, Pourcain, Beate St, Smith, George Davey, Sandy, Jonathan, Relton, Caroline L, Lewis, Sarah J, Hemani, Gibran, Sharp, Gemma C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Future Medicine Ltd 2019
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462847/
https://www.ncbi.nlm.nih.gov/pubmed/30638414
http://dx.doi.org/10.2217/epi-2018-0091
Descripción
Sumario: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.

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