Emory College of Arts & Sciences

Cardio-kidney-metabolic (CKM) diseases represent a major public health challenge, accounting for a large proportion of global burden of morbidity and mortality. These conditions share risk factors, including genetic predisposition, environmental exposures, and lifestyle influences, which collectively drive disease development and progression. Epigenetic modifications, particularly DNA methylation (DNAm), serve as key mediators and biomarkers between these risk factors and disease phenotypes by regulating gene expression without altering the DNA sequence. Epigenome-wide association studies have identified DNAm markers associated with CKM diseases and related phenotypes, highlighting both shared pathways and disease-specific epigenetic signatures in inflammation, metabolic dysfunction, and aging-related processes. Longitudinal studies further demonstrate the dynamic nature of DNAm changes over time, offering insights into disease trajectories. Additionally, methylation risk scores integrating multiple epigenetic markers show promise in improving disease prediction and risk stratification beyond traditional clinical factors. To synthesize the current evidence, we conducted a targeted literature search in PubMed for English-language, peer-reviewed articles published between 2014 and the present. Future research leveraging large, well-phenotyped cohorts, advanced statistical methods, and innovative study designs will be critical for uncovering novel biomarkers, refining risk prediction models, and developing targeted epigenetic therapies to mitigate the global burden.

Dynamic protein post-translational methylation is essential for cellular function, highlighted by the essential role of methylation in transcriptional regulation and its aberrant dysregulation in diseases, including cancer. This underscores the importance of cataloging the cellular methylproteome. However, comprehensive analysis of the methylproteome remains elusive due to limitations in current enrichment and analysis pipelines. Here, we employ an l-methionine analogue, ProSeMet, that is chemoenzymatically converted to the SAM analogue ProSeAM in cells and in vivo to tag proteins with a biorthogonal alkyne that can be directly detected via liquid chromatography and tandem mass spectrometry (LC-MS/MS), or functionalized for subsequent selective enrichment and LC-MS/MS identification. Without enrichment, we identify known and novel lysine mono-, di-, and tripargylation, histidine propargylation, and arginine propargylation with site-specific resolution on proteins including heat shock protein HSPA8, the translational elongation factor eEF1A1, and the metabolic enzyme phosphoglycerate mutase 1, or PGAM1, for which methylation has been implicated in human disease. With enrichment, we identify 486 proteins known to be methylated and 221 proteins with novel propargylation sites encompassing diverse cellular functions. Systemic ProSeMet delivery in mice propargylates proteins across organ systems with blood-brain barrier penetrance and identifies site-specific propargylation in vivo with LC-MS/MS. Leveraging these pipelines to define the cellular methylproteome may have broad applications for understanding the methylproteome in the context of disease.

To estimate associations between the length of state-level eviction moratoria enacted in March and April 2020 in the United States and perinatal outcomes.

We used data from natality files, 2020-2021 to identify individuals with Medicaid or no insurance who conceived in March-May 2020. The exposure was the number of months exposed to a moratorium (0 (referent, no state-level moratoria), 1-2, 3-4, 5 or more). Outcomes included preterm birth (PTB, < 37 weeks gestation), very preterm birth (VPTB, < 32 weeks gestation), low birthweight (LBW, < 2500 g), very low birthweight (VLBW, < 1500 g), primary cesarean, or maternal morbidity. We estimated risk ratios (RRs) using log-binomial regression, including individual, county, and state-level confounders. We conducted several sensitivity analyses to rule out residual state-level confounding including a negative control analysis of 2019 conceptions and difference-in-difference analysis.

We included 375,821 births. Following adjustment, having a moratorium in place for 5 or more months was associated with slightly reduced risk of PTB (RR: 0.95, 95 % CI: 0.88, 1.02), VPTB (RR: 0.90, 95 % CI: 0.8-1.01), LBW (RR: 0.95, 95 % CI: 0.9-1.01), and VLBW (RR: 0.91, 95 % CI: 0.81-1.02) compared to states without a moratorium. There was no association with cesarean or maternal morbidity. Sensitivity analyses showed that all or most of the observed associations may be explained by residual state-level confounding.

State-level eviction moratoria were associated with improved birth outcomes, yet it is likely that all or most of the observed association is due to other policy actions or characteristics of enacting states.