Dataset Information

DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years.

ABSTRACT:

Background

This study assessed the associations between nine differentially methylated regions (DMRs) of imprinted genes in DNA derived from umbilical cord blood leukocytes in males and females and (1) birth weight for gestational age z score, (2) weight-for-length (WFL) z score at 1 year, and (3) body mass index (BMI) z score at 3 years.

Methods

We conducted multiple linear regression in n = 567 infants at birth, n = 288 children at 1 year, and n = 294 children at 3 years from the Newborn Epigenetics Study (NEST). We stratified by sex and adjusted for race/ethnicity, maternal education, maternal pre-pregnancy BMI, prenatal smoking, maternal age, gestational age, and paternal race. We also conducted analysis restricting to infants not born small for gestational age.

Results

We found an association between higher methylation of the sequences regulating paternally expressed gene 10 (PEG10) and anthropometric z scores at 1 year (β = 0.84; 95% CI = 0.34, 1.33; p = 0.001) and 3 years (β = 1.03; 95% CI = 0.37, 1.69; p value = 0.003) in males only. Higher methylation of the DMR regulating mesoderm-specific transcript (MEST) was associated with lower anthropometric z scores in females at 1 year (β = - 1.03; 95% CI - 1.60, - 0.45; p value = 0.001) and 3 years (β = - 1.11; 95% CI - 1.98, - 0.24; p value = 0.01). These associations persisted when we restricted to infants not born small for gestational age.

Conclusion

Our data support a sex-specific association between altered methylation and weight status in early life. These methylation marks can contribute to the compendium of epigenetically regulated regions detectable at birth, influencing obesity in childhood. Larger studies are required to confirm these findings.

SUBMITTER: Gonzalez-Nahm S

PROVIDER: S-EPMC6025828 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years.

Gonzalez-Nahm Sarah S Mendez Michelle A MA Benjamin-Neelon Sara E SE Murphy Susan K SK Hogan Vijaya K VK Rowley Diane L DL Hoyo Cathrine C

Clinical epigenetics 20180628

<h4>Background</h4>This study assessed the associations between nine differentially methylated regions (DMRs) of imprinted genes in DNA derived from umbilical cord blood leukocytes in males and females and (1) birth weight for gestational age <i>z</i> score, (2) weight-for-length (WFL) <i>z</i> score at 1 year, and (3) body mass index (BMI) <i>z</i> score at 3 years.<h4>Methods</h4>We conducted multiple linear regression in <i>n</i> = 567 infants at birth, <i>n</i> = 288 children at 1 year, and ...[more]

PMID: 29988473

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Project description:BackgroundMechanisms responsible for associations between intake of mother's milk in very-low-birth-weight (VLBW, <1500 g) infants and later neurodevelopment are poorly understood. It is proposed that early nutrition may affect neurodevelopmental pathways by altering gene expression through epigenetic modification. Variation in DNA methylation (DNAm) at cytosine-guanine dinucleotides (CpGs) is a commonly studied epigenetic modification.ObjectivesWe aimed to assess whether early mother's milk intake by VLBW infants is associated with variations in DNAm at 5.5 y, and whether these variations correlate with neurodevelopmental phenotypes.MethodsThis cohort study was a 5.5-y follow-up (2016-2018) of VLBW infants born in Ontario, Canada who participated in the Donor Milk for Improved Neurodevelopmental Outcomes trial. We performed an epigenome-wide association study (EWAS) to test whether percentage mother's milk (not including supplemental donor milk) during hospitalization was associated with DNAm in buccal cells during early childhood (n = 143; mean ± SD age: 5.7 ± 0.2 y; birth weight: 1008 ± 517 g). DNAm was assessed with the Illumina Infinium MethylationEPIC array at 814,583 CpGs. In secondary analyses, we tested associations between top-ranked CpGs and measures of early childhood neurodevelopment, e.g., total surface area of the cerebral cortex (n = 41, MRI) and Full-Scale IQ (n = 133, Wechsler Preschool and Primary Scale of Intelligence-IV).ResultsEWAS analysis demonstrated percentage mother's milk intake by VLBW infants during hospitalization was associated with DNAm at 2 CpGs, cg03744440 [myosin XVB (MYO15B)] and cg00851389 [metallothionein 1A (MT1A)], at 5.5 y (P < 9E-08). Gene set enrichment analysis indicated that top-ranked CpGs (P < 0.001) were annotated to genes enriched in neurodevelopmental biological processes. Corroborating these findings, DNAm at several top identified CpGs from the EWAS was associated with cortical surface area and IQ at 5.5 y (P < 0.05).ConclusionsIn-hospital percentage mother's milk intake by VLBW infants was associated with variations in DNAm of neurodevelopmental genes at 5.5 y; some of these DNAm variations are associated with brain structure and IQ.This trial was registered at isrctn.com as ISRCTN35317141 and at clinicaltrials.gov as NCT02759809.

Dataset Information

DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years.

Background

Methods

Results

Conclusion

Publications

DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years.

Similar Datasets

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