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A transcriptomic signature that predicts pre-hypertension in adolescence and higher systolic blood pressure in childhood

ABSTRACT: Suboptimal fetal growth (SFG), being born small-for-gestational-age (SGA), and catch-up (CU) growth are individually and together linked to cardiometabolic (CM) risks. However not all develop adverse outcomes. This study aimed to validate a transcriptomic signature to identify individuals at greatest CM risk. Using National Heart Lung and Blood Institute criteria to define CM risk, healthy and prehypertensive 17-year-olds were identified in the ALSPAC (UK) childhood cohort. Epigenomic and transcriptomic differences were analysed. A hypernetwork identified functionally related genes, which were used in random forest classification to predict prehypertensive phenotypes. The BabyGRO (UK) cohort included 80 children aged 3–7 years, born at term following pregnancies with SFG risks. Anthropometric, CM markers and transcriptomic profiles were collected, fetal and childhood weight trajectories and their relationship to CM markers assessed, and transcriptome used for prediction. CU-SGA individuals in ALSPAC were 1.6 times more likely than all others to be prehypertensive at 17 years (p<1x10⁻⁵). A 42-gene hypernetwork cluster was highly predictive of prehypertension (AUC 0.984, error rate 5.4%). In BabyGRO, 20 of these genes accurately predicted higher systolic blood pressure (AUC 0.971, error rate 3.6%). This transcriptomic signature could help identify children with adverse pre- and postnatal growth who may develop prehypertension.

ORGANISM(S): Homo sapiens

PROVIDER: GSE312011 | GEO | 2025/12/02

REPOSITORIES: GEO

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Project description:Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualised evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analysed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analysed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment. Bisulfite converted DNA of PB from 36 SGA born children treated long-term with rhGH and 18 SGA born children with no rhGH treatment (controls) were hybridized to the Illumina Infinium HumanMethylation 450k Bead Chip.

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A transcriptomic signature that predicts pre-hypertension in adolescence and higher systolic blood pressure in childhood

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