Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years

Abstract

Increases in aortic pulse wave velocity, a measure of arterial stiffness, can lead to elevated systolic blood pressure and increased cardiac afterload in adulthood. These changes are detectable in childhood and potentially originate in utero, where an adverse early life environment can alter DNA methylation patterns detectable at birth. Here, analysis of epigenome-wide methylation patterns using umbilical cord blood DNA from 470 participants in the Southampton’s Women’s Survey identified differential methylation patterns associated with systolic blood pressure, pulse pressure, arterial distensibility, and descending aorta pulse wave velocity measured by magnetic resonance imaging at 8 to 9 years. Perinatal methylation levels at 16 CpG loci were associated with descending aorta pulse wave velocity, with identified CpG sites enriched in pathways involved in DNA repair ( P =9.03×10 −11 ). The most significant association was with cg20793626 methylation (within protein phosphatase, Mg2+/Mn2+ dependent 1D; β=−0.05 m/s/1% methylation change, [95% CI, −0.09 to −0.02]). Genetic variation was also examined but had a minor influence on these observations. Eight pulse wave velocity-linked dmCpGs were associated with prenatal modifiable risk factors, with cg08509237 methylation (within palmitoyl-protein thioesterase-2) associated with maternal oily fish consumption in early and late pregnancy. Lower oily fish consumption in early pregnancy modified the relationship between methylation and pulse wave velocity, with lower consumption strengthening the association between cg08509237 methylation and increased pulse wave velocity. In conclusion, measurement of perinatal DNA methylation signatures has utility in identifying infants who might benefit from preventive interventions to reduce risk of later cardiovascular disease, and modifiable maternal factors can reduce this risk in the child.

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study

“…Although the exact mechanism remains unknown, the earliest signs of CVD could originate already in the developing fetus, possibly mediated through epigenetic mechanisms [ 21 ]. Murray et al reported that maternal risk factors during pregnancy could induce DNA methylation in the offspring’s genome at birth, which in turn, was found to be associated with enhanced arterial stiffening after a follow-up of 8–9 years [ 22 ]. In addition, offspring of mothers with pregestational diabetes have been observed to have an increased risk for pathological ventricular hypertrophy already at birth [ 23 ].…”

Is It in the EPIgenome?: Epigenetics Marks at Birth Are Associated With Arterial Stiffness in Children

“…For example, CpG methylation of these regions in cardiac myocytes inversely correlates with gene expression. 9 As mentioned, Murray et al 3 them aortic pulse wave velocity by magnetic resonance imaging and correlated with CpG methylation. Essentially, 16 CpG loci were identified to be associated with aortic pulse wave velocity, with 8 being associated with prenatal modifiable risk factors of the mother.…”

“…The different epigenetic layers include DNA and histone modifications as well as spatial genome organization and noncoding RNAs. For practical reasons, epigenome-wide association studies, like the one presented by Murray et al, 3 largely focused on DNA methylation, or more precisely on methylation of the cytosine-phosphate-guanine palindrome (CpG). 6 Most methods to detect DNA methylation rely on the conversion of unmethylated cytosine to thymine.…”

Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA

“…Among these, 13 out of 15 suggestive DMRs were positively associated with AIx. The association results of suggestive DMRs and their inclusive CpGs for six AS/PH traits are presented in Supplementary Tables [13][14][15][16][17][18]. Overall, the number of CpGs included in suggestive DMRs ranged from 3 to 7.…”