Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models

Benjamin I. Laufer, Yu Hasegawa, Zhichao Zhang, Casey E. Hogrefe, Laura A. Rosso, Lori Haapanen, Hyeyeon Hwang, Melissa D. Bauman, Judy Van de Water, Ameer Y. Taha, Carolyn M. Slupsky, Mari S. Golub, John P. Capitanio, Catherine A. VandeVoort, Cheryl K. Walker and Janine M. LaSalle ()
Additional contact information
Benjamin I. Laufer: University of California Davis
Yu Hasegawa: University of California Davis
Zhichao Zhang: University of California Davis
Casey E. Hogrefe: University of California Davis
Laura A. Rosso: University of California Davis
Lori Haapanen: University of California Davis
Hyeyeon Hwang: University of California Davis
Melissa D. Bauman: University of California Davis
Judy Van de Water: University of California Davis
Ameer Y. Taha: University of California Davis
Carolyn M. Slupsky: University of California Davis
Mari S. Golub: University of California Davis
John P. Capitanio: University of California Davis
Catherine A. VandeVoort: University of California Davis
Cheryl K. Walker: University of California Davis
Janine M. LaSalle: University of California Davis

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.

Date: 2022
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33162-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33162-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33162-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().