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Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children.

Publication ,  Journal Article
Moylan, CA; Mavis, AM; Jima, D; Maguire, R; Bashir, M; Hyun, J; Cabezas, MN; Parish, A; Niedzwiecki, D; Diehl, AM; Murphy, SK; Abdelmalek, MF; Hoyo, C
Published in: Epigenetics
November 2022

Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90    mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7-12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3-13.4%) and MRE was 2.5 kPa (range, 1.5-3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR<5%). The top two CpGs, cg25474373 and cg07264203, mapped to or near RFTN2 and PRICKLE2 genes. These two CpG sites were also significantly associated with a NAFLD diagnosis. As higher LFC associates with an adverse cardiometabolic profile already in childhood, altered DNAm may identify these children early in disease course for targeted intervention. Larger, longitudinal studies are needed to validate these findings and determine mechanistic relevance.

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Published In

Epigenetics

DOI

EISSN

1559-2308

Publication Date

November 2022

Volume

17

Issue

11

Start / End Page

1446 / 1461

Location

United States

Related Subject Headings

  • Non-alcoholic Fatty Liver Disease
  • Liver
  • Infant, Newborn
  • Humans
  • Developmental Biology
  • DNA Methylation
  • Alanine Transaminase
  • Adolescent
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
 

Citation

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MLA
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Moylan, C. A., Mavis, A. M., Jima, D., Maguire, R., Bashir, M., Hyun, J., … Hoyo, C. (2022). Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children. Epigenetics, 17(11), 1446–1461. https://doi.org/10.1080/15592294.2022.2039850
Moylan, Cynthia A., Alisha M. Mavis, Dereje Jima, Rachel Maguire, Mustafa Bashir, Jeongeun Hyun, Melanie N. Cabezas, et al. “Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children.Epigenetics 17, no. 11 (November 2022): 1446–61. https://doi.org/10.1080/15592294.2022.2039850.
Moylan CA, Mavis AM, Jima D, Maguire R, Bashir M, Hyun J, et al. Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children. Epigenetics. 2022 Nov;17(11):1446–61.
Moylan, Cynthia A., et al. “Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children.Epigenetics, vol. 17, no. 11, Nov. 2022, pp. 1446–61. Pubmed, doi:10.1080/15592294.2022.2039850.
Moylan CA, Mavis AM, Jima D, Maguire R, Bashir M, Hyun J, Cabezas MN, Parish A, Niedzwiecki D, Diehl AM, Murphy SK, Abdelmalek MF, Hoyo C. Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children. Epigenetics. 2022 Nov;17(11):1446–1461.

Published In

Epigenetics

DOI

EISSN

1559-2308

Publication Date

November 2022

Volume

17

Issue

11

Start / End Page

1446 / 1461

Location

United States

Related Subject Headings

  • Non-alcoholic Fatty Liver Disease
  • Liver
  • Infant, Newborn
  • Humans
  • Developmental Biology
  • DNA Methylation
  • Alanine Transaminase
  • Adolescent
  • 3105 Genetics
  • 3101 Biochemistry and cell biology