Homeostatic inflammation in the placenta is protective against adult cardiovascular and depressive outcomes
Fitzgerald, E.; Shen, M. J.; Yong, H.; Wang, Z.; Pokhvisneva, I.; Patel, S.; O'Toole, N.; Chan, S.-y.; Chen, H.; Gluckman, P.; Chan, J. K.; Lee, P.; Meaney, M.
Show abstract
Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an expression signature of homeostatic inflammation in the term placenta and use expression quantitative trait loci (eQTLs) to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we carried out a phenome-wide association study, followed by mendelian randomization and identified protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth were also over-represented within the module. Our data support a model where disruption of placental homeostatic inflammation, following preterm birth or intra-amniotic infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals. Finally, we identify aspirin as a putative modulator of this homeostatic inflammatory signature.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The genetic and phenotypic correlates of neonatal Complement Component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders 96%
- Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts 95%
- eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis 95%
Similar papers in this journal
Similar papers in this journal
- Immunological Drivers and Potential Novel Drug Targets for Major Psychiatric, Neurodevelopmental, and Neurodegenerative Conditions 94%
- Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium 94%
- Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records 93%
Similar papers in this journal
- Disentangling mechanisms behind the pleiotropic effects of proximal 16p11.2 BP4-5 CNVs 96%
- Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension 95%
- Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity 95%
Similar papers in this journal
- Maternal obesity and offspring neurodevelopment are associated with hypoxic gene expression in term human placenta 97%
- Sex-dependent placental mQTL provide insight into the prenatal origins of childhood-onset traits and conditions 96%
- Signatures Of TSPAN8 Variants Associated With Human Metabolic Regulation And Diseases 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.