Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate. (14th January 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Epigenomics. Volume 11:Number 2(2019)
• Page Start: 133
• Page End: 145
• Publication Date: 2019-01-14
• Subjects: ALSPAC -- epigenetics -- mendelian randomization -- nsCL/P; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2018-0091
• Languages: English
• ISSNs: 1750-1911

Abstract

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.