DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years

Sarah Gonzalez-Nahm, Michelle A. Mendez, Sara E. Benjamin-Neelon, Susan K. Murphy, Vijaya K. Hogan, Diane L. Rowley, Cathrine Hoyo

This study assessed the associations between nine differentially methylated regions (DMRs) of imprinted genes in DNA derived from umbilical cord blood leukocytes in males and females and (1) birth weight for gestational age z score, (2) weight-for-length (WFL) z score at 1 year, and (3) body mass index (BMI) z score at 3 years. We conducted multiple linear regression in n = 567 infants at birth, n = 288 children at 1 year, and n = 294 children at 3 years from the Newborn Epigenetics Study (NEST). We stratified by sex and adjusted for race/ethnicity, maternal education, maternal pre-pregnancy BMI, prenatal smoking, maternal age, gestational age, and paternal race. We also conducted analysis restricting to infants not born small for gestational age. We found an association between higher methylation of the sequences regulating paternally expressed gene 10 (PEG10) and anthropometric z scores at 1 year (β = 0.84; 95% CI = 0.34, 1.33; p = 0.001) and 3 years (β = 1.03; 95% CI = 0.37, 1.69; p value = 0.003) in males only. Higher methylation of the DMR regulating mesoderm-specific transcript (MEST) was associated with lower anthropometric z scores in females at 1 year (β = - 1.03; 95% CI - 1.60, - 0.45; p value = 0.001) and 3 years (β = - 1.11; 95% CI - 1.98, - 0.24; p value = 0.01). These associations persisted when we restricted to infants not born small for gestational age. Our data support a sex-specific association between altered methylation and weight status in early life. These methylation marks can contribute to the compendium of epigenetically regulated regions detectable at birth, influencing obesity in childhood. Larger studies are required to confirm these findings.