Discussion
drug addiction, inflammation, neuropsychiatric and cardiovascular morbidities, infections, psychiatric, placenta-brain
INFLAMMATION, PRENATAL STRESS, INFECTIONS, DISORDERS
In this first report of epigenetic signatures of social support in human placentas, we found that the level of prenatal social support during the first trimester of pregnancy is associated with differential methylation of seven CpGs in placenta at delivery. We also identified an additional 42 social support-associated CpGs in placenta dependent on fetal sex. The social support-associated epigenetic signatures in placenta are independent of prenatal stress; hence, social support may have impact on placental methylation even when maternal stress levels are not high. The association between placental expressions of A positive effect of social support on health and well-being even under low stress environment has long been recognized [The enrichment of pathways related to the immune system and cytokines supports shared mechanisms for the potential effects of social support, stress, infections, and other factors. A meta-analytic review has found evidence supporting the link between low social support and inflammation [The placenta has functional roles in fetal neurodevelopment via the “placenta-brain axis,” with potential programming for future mental health outcomes [On the other hand, research suggests that Our findings indicate sex-specific responses of placental epigenome to prenatal social environment. Nevertheless, pathway analyses revealed convergence in enrichment of canonical pathways such as those related to the immune system for the genes annotated to the top 100 social support associated CpGs in pregnancies with male and female fetuses. Studies have previously demonstrated that epigenetic programming of placenta occurs in a sex-dependent manner [We acknowledge the following limitations arising from our design. First, our study may have been underpowered to detect additional associations because of relatively small sample size, particularly for subgroup and gene expression analyses. However, the post hoc power estimates indicate that most of the DNA methylation effect sizes were adequately powered. Second, the participants were selected to study low risk pregnancy, and this may have led to exclusion of individuals with low social support, e.g., individuals with drug addiction or psychiatric disorders. Finally, the level of social support may have changed later during pregnancy. Despite these limitations, we found novel CpGs in placenta associated with social support which withstood correction for multiple testing and adjustment for several important confounders, including estimates of placental cell composition and genetic ancestry. Our data support placental epigenetic programming effect of social support in racially diverse pregnant women with implications for offspring neuropsychiatric and cardiometabolic health. These findings need to be interpreted in the light of the shared genetic risk between loneliness, neuropsychiatric and cardiovascular morbidities [