Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth
Timothy P. York, Shawn J. Latendresse, Colleen Jackson‐Cook, Dana M. Lapato, Sara Moyer, Aaron R. Wolen, Roxann Roberson‐Nay, K. Elizabeth, Susan K. Murphy, Cathrine Hoyo, Bernard F. Fuemmeler, Jerome F. Strauss
Abstract
gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.