| Zdroj: |
Richmond, R, Sharp, G, Herbert, G, Atkinson, C, Taylor, C, Bhattachrya, S, Campbell, D, Hall, M, Kazmi, N, Gaunt, T, McArdle, W, Ring, S, Davey Smith, G, Ness, A R & Relton, C 2018, ' The long-term impact of folic acid in pregnancy on offspring DNA methylation : follow-up of the Aberdeen folic acid supplementation trial (AFAST) ', International Journal of Epidemiology, vol. 47, no. 3 . https://doi.org/10.1093/ije/dyy032 |
| Popis: |
Background It has been proposed that maternal folic acid supplement use may alter DNA methylation patterns of the offspring during the in utero period, which could influence development and later life health outcomes. Evidence from human studies suggests a role of prenatal folate levels in influencing DNA methylation in early life, but this has not been extended to consider persistent effects into adulthood. Methods To better elucidate the long-term impact of maternal folic acid in pregnancy on DNA methylation in offspring, we carried out an epigenome-wide association study (EWAS) nested within the Aberdeen Folic Acid Supplementation Trial (AFAST – a trial of two different doses, 0.2mg and 5mg, folic acid versus placebo). Offspring of the AFAST participants were recruited at a mean age of 47 years and saliva samples were profiled on the Illumina Infinium Human Methylation450 array. Both single site and differentially methylated region analysis were performed. Results We found an association at cg09112514 (p=4.03x10-9 28 ), a CpG located in the 5’ untranslated region of PDGFRA, in the main analysis comparing the intervention arms (low (0.2mg) and high dose (5mg) folic acid combined (N=43)) versus placebo (N=43). Furthermore, a dose-response reduction in methylation at this site was identified in relation to the intervention. In the regional approach, we identified 46 regions of the genome which were differentially methylated in response to the intervention (Sidak P-value |
