Differential methylation at novel putative imprinting control regions on chromosome 20 associated with childhood obesity

Imprinting control regions (ICRs) regulate parent-of-origin gene expression and are enriched for growth and metabolic genes, representing strong candidates for developmental programming of obesity.

In 586 participants of the Newborn Epigenetics STudy (NEST), we leveraged the novel Human Imprintome Array to measure methylation at >1,000 characterized and putative ICRs genome-wide in umbilical cord blood. We applied principal component and kernel machine regression to identify ICR methylation at birth associated with sustained childhood obesity, defined as BMI ≥ 95th percentile during most of childhood. Sustained childhood obesity was associated with differential methylation at seven ICRs in cord blood, with 2–10% mean differences between obesity and normal weight groups, including novel regions localized to chromosome 20q11.1-20q11.21 (ICR_1182, ICR_1179, ICR_1181, ICR_1177, ICR_1180, and ICR_1165), mapping to or near <i>CDC27P4, LINC01597, DUX4L37</i>, and <i>DUX4L34</i>, and ICR_927 mapping to previously characterized <i>ZNF597/NAA60</i>.