Newborn Umbilical Cord Blood DNA Methylation and Gene Expression Levels Exhibit Limited Association with Birth Weight

Most cases of fetal growth retardation are unexplained. These newborns are at high risk of serious illness or death in the neonatal period and exhibit significantly increased risk of specific chronic illnesses later in life. While there are several hypotheses to explain the well-established association between low birth weight and later risk of disease, the true etiology is unknown. To search for molecular patterns that may explain the biological basis for reduced fetal growth in a clinically normal cohort, and possibly provide clues for the lifelong increased risk of disease, we surveyed genome-wide DNA methylation and gene expression patterns in the umbilical cord blood of newborns born in Shelby County, TN. While we did not find genome-wide significant associations of birth weight with either leukocytic gene expression or DNA methylation, we did find suggestive associations in several genes with known effects on pre- or postnatal growth and health. As with previous molecular epidemiological studies of birth weight, we did not sample the most biologically relevant tissues in the newborn. However, our discovery of biologically plausible associations in a peripheral tissue suggests that further studies of tissues key to fetal growth regulation are warranted.