Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at both the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human MethylationEPIC array we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women's Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p≤6.45x10-8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195g (95%CI: -241, -149g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin releasing hormone binding protein (CRHBP).. Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p=1.37x10-255), maternal smoking (7.71%, p=1.50x10-57) and maternal plasma folate levels during pregnancy (0.33%, p=0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and/or suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.

Original publication

DOI

10.1080/15592294.2021.1908706

Type

Journal article

Journal

Epigenetics

Publication Date

30/03/2021

Keywords

Birthweight, DNA methylation, early life environment, pregnancy