Multi-omic Brain and Behavioral Correlates of Cell-free Fetal DNA Methylation in Macaque Maternal Obesity Models

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 21

PMID 36130949

Authors

Benjamin I Laufer

Yu Hasegawa

Zhichao Zhang

Casey E Hogrefe

Laura A Del 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

Janine M LaSalle

Affiliations

Soon will be listed here.

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.

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