There is increasing evidence that metabolic diseases originate in early life, and epigenetic changes have been implicated as key drivers of this early life programming. This led to the hypothesis that epigenetic marks present at birth may predict an individual’s future risk of obesity and type 2 diabetes. In this study, we assessed whether epigenetic marks in blood of newborn children were associated with body mass index (BMI) and insulin sensitivity later in childhood.
DNA methylation was measured in neonatal blood spot samples of 438 children using the Illumina Infinium 450 k BeadChip. Associations were assessed between DNA methylation at birth and BMI z-scores, body fat mass, fasting plasma glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) at age 5 years, as well as birth weight, maternal BMI and smoking status.
No individual methylation sites at birth were associated with obesity or insulin sensitivity measures at 5 years. DNA methylation in 69 genomic regions at birth was associated with BMI z-scores at age 5 years, and in 63 regions with HOMA-IR. The methylation changes were generally small (<5%), except for a region near the non-coding RNA nc886 (VTRNA2-1) where a clear link between methylation status at birth and BMI in childhood was observed (P=0.001). Associations were also found between DNA methylation, maternal smoking and birth weight.
We identified a number of DNA methylation regions at birth that were associated with obesity or insulin sensitivity measurements in childhood. These findings support the mounting evidence on the role of epigenetics in programming of metabolic health. Whether many of these small changes in DNA methylation are causally related to the health outcomes, and of clinical relevance, remains to be determined, but the nc886 region represents a promising obesity risk marker that warrants further investigation.
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This work was supported by the Science and Industry Endowment Fund (RP03-064), Diabetes Australia, and the National Health and Medical Research Council of Australia (NHMRC) (349301, 570109, APP1004211 to BSM, APP1046207 to RAG, APP1061074 to MM) and National Institutes of Health grant R35 CA 209859 to PJ.
MM serves on scientific advisory boards for Fonterra and RAG serves on scientific advisory boards for Fonterra and Ferrero. BSM serves on the scientific advisory board for Nestle and has given lectures on maternal nutrition for Aspen Nutrition and Danone Nutricia. Associated honoraria for MM, RAG and BSM are paid their institutions to support conference travel and continuing education for postgraduate students and early career researchers. PJ is a paid consultant for Zymo, Inc. The remaining authors declare no conflict of interest.
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van Dijk, S., Peters, T., Buckley, M. et al. DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood. Int J Obes 42, 28–35 (2018). https://doi.org/10.1038/ijo.2017.228
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