Blood and adipose tissue DNA methylation in adults born preterm with a very low birth weight–a sibling comparison study

Abstract

Background: Preterm birth and very low birth weight (VLBW; <1500 g) increase risks for poor health outcomes, potentially mediated by epigenetic modifications such as DNA methylation (DNAm). We hypothesized that DNAm differs between VLBW adults and their siblings in blood and adipose tissue. Methods: We studied 75 adults born preterm with VLBW and 73 same-sex sibling controls from the Adults Born Preterm Sibling Study. DNAm at cytosine–guanine dinucleotide (CpG) sites in blood and adipose tissue was assessed using Illumina EPIC 850K at a mean age of 29 years. Biological pathways were investigated with QIAGEN ingenuity pathway analysis (IPA). Results: No differences were observed in blood DNAm. In adipose tissue, 458 CpG sites were differentially methylated (FDR p < 0.05) between VLBW and siblings. Top sites were annotated to genes related to lipid metabolism (cg00264176 (FADS2), 0.077 (0.007), FDR p = 3.24 × 10−14) and neural development (cg08277679 (KIF26A), 0.053 (0.005), FDR p = 8.22 × 10−12). IPA identified enrichment for 81 pathways (FDR p < 0.05). Conclusion: Our results suggest tissue-specific DNAm differences in VLBW adults compared to their siblings. The changes cluster in pathways related to lipid metabolism, neurodevelopment, and cardiometabolic regulation, suggesting lasting tissue-specific epigenetic modifications in VLBW adults.