Maternal Lipodome Across Pregnancy is Associated with the Neonatal DNA Methylome

Abstract

Aim: To classify the association between the maternal lipidome and DNA methylation in cord blood leukocytes. Materials&methods: Untargeted lipidomics was performed on first trimester maternal plasma (M1) and delivery maternal plasma (M3) in 100 mothers from the Michigan Mother-Infant Pairs cohort. Cord blood leukocyte DNA methylation was profiled using the Infinium EPIC bead array and empirical Bayes modeling identified differential DNA methylation related to maternal lipid groups. Results: M3-saturated lysophosphatidylcholine was associated with 45 differentially methylated loci and M3-saturated lysophosphatidylethanolamine was associated with 18 differentially methylated loci. Biological pathways enriched among differentially methylated loci by M3 saturated lysophosphatidylcholines were related to cell proliferation and growth. Conclusion: The maternal lipidome may be influential in establishing the infant epigenome.

Keywords::

• developmental epigenetics
• DNA methylation
• epigenome-wide association studies
• lipidomics
• lysophospholipids
• pregnancy
• umbilical cord blood

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0234

Acknowledgments

We would like to acknowledge the members of the Michigan Regional Comprehensive Metabolomics Resource Core, T Soni and TM Rajendiran, for their assistance in the processing of the lipidomics data. We would like to acknowledge M Puttabyatappa, S Milewski and S Rogers for help with recruitment and processing of samples.

Financial&competing interests disclosure

University of Michigan NIEHS/EPA Children’s Environmental Health and Disease Prevention Center P01 ES022844/RD 83543601 (V Padmanabhan, DC Dolinoy, PXK Song and JM Goodrich), the Michigan Regional Comprehensive Metabolomics Resource Core (MRC2) U24 DK097153 (CF Burant); NIH Children’s Health Exposure Analysis Resource (CHEAR), 1U2C ES026553 (DC Dolinoy, JM Goodrich and CF Burant), Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center P30 ES017885 (V Padmanabhan, DC Dolinoy, JM Goodrich, PXK Song and CF Burant), NIH/NIEHS UG3 OD023285 (V Padmanabhan and DC Dolinoy), Molecular Phenotyping Core, Michigan Nutrition and Obesity Center P30 DK089503 (CF Burant and DC Dolinoy) and Michigan Regional Metabolomics Resource Core R24 DK097153 (CF Burant), and The A. Alfred Taubman Research Institute (CF Burant). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Data described in the manuscript, code book, and analytic code will be made available upon request. Metabolomics data is available at the National Metabolomics Data Repository (metabolomicsworkbench.org/data/index.php).

Additional information

Funding

University of Michigan NIEHS/EPA Children’s Environmental Health and Disease Prevention Center P01 ES022844/RD 83543601 (V Padmanabhan, DC Dolinoy, PXK Song and JM Goodrich), the Michigan Regional Comprehensive Metabolomics Resource Core (MRC2) U24 DK097153 (CF Burant); NIH Children’s Health Exposure Analysis Resource (CHEAR), 1U2C ES026553 (DC Dolinoy, JM Goodrich and CF Burant), Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center P30 ES017885 (V Padmanabhan, DC Dolinoy, JM Goodrich, PXK Song and CF Burant), NIH/NIEHS UG3 OD023285 (V Padmanabhan and DC Dolinoy), Molecular Phenotyping Core, Michigan Nutrition and Obesity Center P30 DK089503 (CF Burant and DC Dolinoy) and Michigan Regional Metabolomics Resource Core R24 DK097153 (CF Burant), and The A. Alfred Taubman Research Institute (CF Burant). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.