hrp0095fc10.2 | GH and IGFs | ESPE2022

The first-year growth response to once-weekly growth hormone (GH) treatment can be predicted from the pre-treatment blood transcriptome in children with GH deficiency (GHD)

Garner Terence , Clayton Peter , Murray Philip , Bagci Ekaterine , Højby Michael , Stevens Adam

Growth response to daily GH treatment can be predicted using pre-treatment gene expression profiles.1 Once-weekly GH treatment potentially reduces the burden of daily injections2 and thus may be a major advancement in care for patients with GHD, vs standard, daily GH treatment. Here we investigate the prediction of first-year growth response based on pre-treatment blood transcriptome in children with GHD undergoing treatment with daily or once-weekly GH. ...

hrp0095p2-129 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2022

Molecular pathways linking fetal growth restriction to cardiometabolic risk in childhood

Perchard Reena , Higgins Lucy , Garner Terence , Stevens Adam , Johnstone Edward , Clayton Peter

Background: Cardiometabolic (CM) risk is linked to being small for gestational age (SGA, birthweight <-2SDS). Fetal growth restriction (FGR) may not result in SGA. We focused on potential CM risk in children born following pregnancies at higher risk for FGR.Aims: To identify associations between fetal and childhood weight trajectory quartiles and CM risk markers. 2.To define molecular pathways potentially associated w...

hrp0092fc12.4 | Growth and Syndromes (to include Turner Syndrome) | ESPE2019

Integration of Transcriptomic and Epigenomic Data in Childhood Identifies a Subset of Individuals Born Small for Gestational Age (SGA) with "catch-up" Growth Who Become Pre-Hypertensive in Early Adulthood

Garner Terence , Murray Philip , Sellers Robert , Whatmore Andrew , Clayton Peter , Stevens Adam

Background: Children born SGA are known to develop cardiometabolic conditions in adulthood1. Nothing is known about the relationship of the transcriptome (gene expression) and epigenome (DNA methylation) to birth size and the future development of cardiometabolic disease.Aim: To identify, I) differences and functional links between epigenome age-7years, transcriptome age-9years associated and ...

hrp0092fc12.6 | Growth and Syndromes (to include Turner Syndrome) | ESPE2019

An Integrated Systems Biology Analysis of the Genome, Epigenome and Transcriptome Identifies a Distinct Pattern of Hypermethylation Associated with Low Childhood Growth

Garner Terence , Sellers Robert , Guo Hui , Whatmore Andrew , Clayton Peter , Stevens Adam , Murray Philip

Background: Current data from genome wide association studies (GWAS) explains 24.6% of the variation in adult height from 3290 single nucleotide polymorphisms (SNPs)1. Data on the genetic control of growth velocity during childhood is more limited and no previous studies have linked childhood growth to changes in the transcriptome (gene expression) or epigenome (DNA methylation). Here we present a systems biology approach to understand mid-child...

hrp0094p2-239 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) | ESPE2021

Antenatal Markers Related to Fetal Growth Restriction Can Predict Childhood Systolic Blood Pressure

Perchard Reena , Higgins Lucy , Garner Terence , Stevens Adam , Johnstone Edward , Clayton Peter ,

Background: Being born small for gestational age (SGA) is linked with higher systolic blood pressure (SBP). Fetuses with growth restriction (FGR) may be either SGA or appropriate size for gestational age at birth. However, it is not known which factors contributing to size at birth influence the relationship with SBP.Aim: To determine whether antenatal markers of FGR can predict the upper quartile of childhood SBP.<p...

hrp0097rfc4.1 | Growth and syndromes (to include Turner syndrome) | ESPE2023

Functional networks reveal pathways linking early growth to childhood blood pressure in the Manchester BabyGRO Study

Perchard Reena , Garner Terence , Stevens Adam , Higgins Lucy , Johnstone Edward , Clayton Peter

Background: Many studies have associated being born small for gestational age (SGA) [and by implication having suboptimal fetal growth (SFG)] to childhood cardiometabolic risk markers. However, not all growth-restricted pregnancies result in SGA. In the Manchester BabyGRO study, we focussed on pregnancies at risk of SFG with most babies born AGA, and using transcriptomic and metabolomic data we have identified pathways related to higher child systolic blood pr...

hrp0097t19 | Section | ESPE2023

Pre-treatment Blood Transcriptome Predicts Growth Response to Somapacitan Treatment in Children Born Small for Gestational Age

Garner Terence , Clayton Peter , Højby Rasmussen Michael , Murray Philip , Stevens Adam

Treating short stature in children born small for gestational age (SGA) requires daily growth hormone (GH) injections that are burdensome for patients and caregivers. Results from REAL5 (ongoing randomised, multinational, open-label, controlled, dose-finding phase 2 trial; NCT03878446) indicate that somapacitan (0.24 mg/kg/week) has an efficacy, safety, and tolerability profile similar to daily GH (0.067 mg/kg/day) after 52 weeks of treatment in children born SGA. Predicting G...

hrp0092fc12.5 | Growth and Syndromes (to include Turner Syndrome) | ESPE2019

Integrated Analysis of Baseline Blood Transcriptome and Genome Identifies Clusters of Turner Syndrome Patients with Different Responses to Recombinant Human Growth Hormone

Sellers Robert , Amin Amina , Patel Kajal , Garner Terence , Whatmore Andrew , Koledova Ekaterina , Murray Philip , Chatelain Pierre , Clayton Peter , Stevens Adam

Responsiveness to recombinant human growth hormone (rhGH) treatment in Turner syndrome (TS) is highly variable. Previous research has characterised genetic variants associated with rhGH response but these only have a minor impact. The relationship of these genetic variants to the blood transcriptome is unknown. The aim of this analysis was to relate unsupervised baseline blood transcriptome and genetic data from TS patients to their phenotype, karyotype and responsiveness to r...

hrp0097p1-480 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2023

Grb10a Knockdown in Early Life Permanently Alters Growth, Cardiometabolic Phenotype, and the Co-ordination of the Whole Transcriptome in Zebrafish

Evans Bridget , Garner Terence , De Leonibus Chiara , Wearing Oliver , Shiels Holly , Hurlstone Adam , Clayton Peter , Stevens Adam

The ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis encapsulates the relationship between pre- and perinatal exposures causing altered growth and the development of later life disease. Mediators of this relationship have not been fully defined. We have used zebrafish [ZF] (Danio rerio) as a potential model for DOHaD, modifying expression of grb10a, an adapter protein that interacts with the insulin and IGF receptors, to act as a negative r...