PT  - JOURNAL ARTICLE
AU  - Benjamin I. Laufer
AU  - Yu Hasegawa
AU  - Zhichao Zhang
AU  - Casey E. Hogrefe
AU  - Laura A. Del Rosso
AU  - Lori Haapanan
AU  - Hyeyeon Hwang
AU  - Melissa D. Bauman
AU  - Judy A. Van de Water
AU  - Ameer Y. Taha
AU  - Carolyn M. Slupsky
AU  - Mari S. Golub
AU  - John P. Capitanio
AU  - Catherine A. VandeVoort
AU  - Cheryl K. Walker
AU  - Janine M. LaSalle
TI  - Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models
AID  - 10.1101/2021.08.27.457952
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.27.457952
4099  - http://biorxiv.org/content/early/2021/08/28/2021.08.27.457952.short
4100  - http://biorxiv.org/content/early/2021/08/28/2021.08.27.457952.full
AB  - 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. Ultimately, maternal obesity altered infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic biomarkers.Competing Interest StatementThe authors have declared no competing interest.