Serum discrimination and phenotype assessment of coronary artery disease patents with and without type 2 diabetes prior to coronary artery bypass graft surgery

Hocker, James R.; Lerner, Megan R.; Lightfoot, Stan; Peyton, Marvin D.; Thompson, Jess L.; Deb, Subrato; Reinersman, Mathew; Hanas, Rushie J.; Postier, Russel; Edil, Barish H.; Burkhart, Harold M.; Hanas, Jay S.

doi:10.1371/journal.pone.0234539

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…They found higher methylation at cg05825244 in EBF4 (among our 12 CpGs differentially methylated in VLBW adults), which was associated with a 23% increased risk of acute coronary syndromes. Further, mass spectrometry of sera from patients about to undergo coronary artery bypass graft (CABG) surgery identified that presence of EBF4 protein was more prevalent and helped distinguish patients with T2DM [ 67 ]. Our gene network analysis identified that in VLBW adults EBF4 is a key gene in a network centering on the serine/threonine protein kinase, Akt , which has key roles in many signaling pathways [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2023

View full text Add to dashboard Cite

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DNA Methylation Patterns At Birth Predict Health Outcomes In Young Adults Born Very Low Birthweight

Cameron

Jones

Horwood

et al. 2022

Preprint

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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 analysed 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 analysed on Illumina Infinium MethylationEPIC 850K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by logistic 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, top CpGs featuring clusters in ARID3A, SPATA33, and PLCH1. The canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling (p = 3.44E− 11) and 15 of the 20 CpGs most different between VLBW cases and controls showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). At 28 years, 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 direction 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 multiple 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.

show abstract

Serum discrimination and phenotype assessment of coronary artery disease patents with and without type 2 diabetes prior to coronary artery bypass graft surgery

Cited by 2 publications

References 43 publications

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

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

DNA Methylation Patterns At Birth Predict Health Outcomes In Young Adults Born Very Low Birthweight

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