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Publication - Professor Tom Gaunt

    Hypertensive disorders of pregnancy and DNA methylation in newborns: Findings from the PACE Consortium

    Citation

    Kazmi, N, Sharp, G, Reese, S, Vehmeijer, F, Lahti, J, Page, CM, Zhang, W, Rifas-Shiman, SL, Rezwan, FI, Simpkin, A, Burrows, K, Richardson, T, Ferreira, DDS, Fraser, A, Harmon, Q, Zhao, S, Jaddoe, V, Czamara, D, Binder, EB, Magnus, M, Håberg, S, Nystad, W, Nohr, EA, Starling, AP, Kechris, KJ, Yang, IV, DeMeo, D, Litonjua, A, Baccarelli, A, Oken, E, Holloway, JW, Karmaus, W, Arshad, S, Dabelea, D, Sørensen, T, Laivuori, H, Räikkönen, K, Felix, JF, London, SJ, Hivert, M-F & others 2019, ‘Hypertensive disorders of pregnancy and DNA methylation in newborns: Findings from the PACE Consortium’. Hypertension.

    Abstract

    Hypertensive disorders of pregnancy (HDP) are associated with low birthweight, shorter gestational age and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy And Childhood Epigenetics (PACE) Consortium to test the association between either maternal HDP (ten cohorts; n=5242 (cases=476)) or pre-eclampsia (PE; three cohorts; n=2219 (cases=135)) and epigenome-wide DNA methylation in cord-blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and PE were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites and across all 43 sites mean absolute difference in methylation was between 0.6 to 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of PE with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in one study (n=108 HPD cases, 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

    Full details in the University publications repository