Maternal obesity and gestational weight gain are modestly associated with umbilical cord DNA methylation.
INTRODUCTION
Maternal obesity (OB) and excessive gestational weight gain (GWG) are strong independent contributors that augment obesity risk in offspring. However, direct evidence of epigenetic changes associated with maternal habitus remains sparse.


METHODS
We utilized Bisulfite Amplicon Sequencing (BSAS) to conduct targeted DNA methylation association analysis of maternal obesity and excessive GWG with DNA methylation of select metabolism-related and imprinted genes. Umbilical cord (UC) tissue from infants born to normal weight and overweight/obese women from the Glowing study were utilized (n = 78).


RESULTS
In multivariable linear regression adjusted for relevant confounders, Institute on Medicine (IOM) GWG category and infant sex were significantly associated with UC IGFBP1 methylation, while gestation length was significantly associated with UC PRKAA1 methylation. In addition, infant fat mass (%) at 2 weeks of age was significantly associated with umbilical cord methylation of RAPTOR. While regression tree analysis confirmed findings from multivariable models demonstrating that maternal early pregnancy BMI and IOM GWG category are associated with fetal UC DNA methylation patterns for select metabolic and imprinted genes, in general, effect sizes were quite small and statistical significance was not maintained when accounting for multiple testing.


DISCUSSION
Our findings suggest that maternal obesity and excessive GWG are weakly correlated with offspring DNA methylation patterns at birth.
['Thakali|Keshari M|KM|', 'Faske|Jennifer B|JB|', 'Ishwar|Arjun|A|', 'Alfaro|Maria P|MP|', 'Cleves|Mario A|MA|', 'Badger|Thomas M|TM|', 'Andres|Aline|A|', 'Shankar|Kartik|K|']
D055372:AMP-Activated Protein Kinases D015331:Cohort Studies D019175:DNA Methylation D005260:Female D006801:Humans D007231:Infant, Newborn D018970:Insulin-Like Growth Factor Binding Protein 1 D008297:Male D009765:Obesity D011247:Pregnancy D011248:Pregnancy Complications D011506:Proteins D012044:Regression Analysis D000076223:Regulatory-Associated Protein of mTOR D014470:Umbilical Cord D015430:Weight Gain
Obesity DNA methylation Epigenetics Developmental programming