SEARCHCOHORTcardiology, epidemiology

cohort·cardiology, epidemiology, pediatrics, pulmonology, biomedical research·PMC10035230

DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight

Clinical Epigenetics · 13 authors, 5 centres

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TL;DR

This longitudinal cohort study analyzed DNA methylation at birth and at 28 years in individuals born very low birthweight (VLBW) versus controls. It found that neonatal methylation differences were associated with adult cardiovascular and respiratory traits.

Full summary

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The study analyzed genomic DNA from archived neonatal blood spots (109 VLBW, 51 controls) and adult peripheral blood (~28 years; 215 VLBW, 96 controls) using Illumina MethylationEPIC arrays. Linear regression identified differentially methylated CpGs between groups, with genome-wide significance set to p<0.05 (FDR-adjusted). In neonates, over 16,400 CpGs differed, with the top pathway being Cardiac Hypertrophy Signaling. In adults, 12 CpGs differed, including in EBF4 and HIF3A. Four CpGs differed at both ages, with three reversing direction. Neonatal methylation at cg16426670 in EBF4 was associated with multiple adult cardiovascular traits. The findings suggest neonatal methylation may predict future adult cardiovascular health.

STUDY TYPE

cohort

SPECIALTY

cardiology

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AI pipeline

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ORIGINAL PAPER

PMC10035230

DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight

Clinical Epigenetics

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ABSTRACT

Background Individuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function and respiratory outcomes at age 28 years were documented. Results Genomic DNA from archived newborn heel-prick blood ( n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years ( n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p < 0.05 adjusted for false discovery rate (FDR, Benjamini-Hochberg). In neonates, methylation at over 16,400 CpG methylation sites differed between VLBW cases and controls and the canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling ( p = 3.44E −11 ). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A , SPATA33 , and PLCH1 and these 3 genes, along with MCF2L , TRBJ2 -1 and SRC , led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1 . DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults. Conclusions These findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-023-01463-3.

CITATION EXPORT

Vicky A. Cameron, Gregory T. Jones, L. John Horwood et al.. DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight. Clinical Epigenetics. (2023). https://doi.org/10.1186/s13148-023-01463-3

AUTHORS

13 · 5 CENTRES

Vicky A. Cameron, Gregory T. Jones, L. John Horwood, Anna P. Pilbrow, Julia Martin, Chris Frampton, Wendy T. Ip, Richard W. Troughton, Charlotte Greer, Jun Yang, Michael J. Epton, Sarah L. Harris, Brian A. Darlow

1grid.29980.3a0000 0004 1936 7830Christchurch Heart Institute, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, 8140 New Zealand
2grid.29980.3a0000 0004 1936 7830Department of Surgical Sciences, University of Otago, Dunedin, New Zealand
3grid.29980.3a0000 0004 1936 7830Christchurch Health and Development Study, Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
4grid.29980.3a0000 0004 1936 7830Department of Paediatrics, University of Otago, Christchurch, New Zealand
5grid.414299.30000 0004 0614 1349Respiratory Physiology Laboratory, Christchurch Hospital, Christchurch, New Zealand