Clinical Epigenetics

BackgroundSmoking is a major preventable risk factor for all-cause mortality and disability worldwide. It leads to age-related diseases, but the effects and reversibility of smoking behaviors on different epigenetic clocks are not fully explored. ObjectiveTo characterize the association of epigenetic age acceleration in whole blood with active and secondhand smoking (SHS), smoking intensity, and time since cessation among U.S. adults. MethodsThis is a cross-sectional study in adults from the N...

Epigenetic clocks and scores have been investigated as potential biomarkers of later-life health outcomes following early-life exposures. In pediatric settings, DNA methylation (DNAm) is often measured in saliva; however, most clocks and scores have been trained in adult blood. Therefore, we assessed the performance, correlation, longitudinal stability, and association with early-life adversity (ELA) for established epigenetic measures in matched pediatric blood and saliva samples. Leveraging th...

IntroductionEarly-life adversity (ELA) encompasses a range of environmental stressors, including physical, emotional, and social challenges that can affect health during the critical early developmental period. Extensive research has linked ELA to negative long-term health outcomes, yet the underlying biological mechanisms remain poorly understood. The current study investigates how early institutional care changes the epigenetic landscape in young adults. The study also provides insights into r...

Child maltreatment is a leading cause of pediatric morbidity and mortality, potentially propagated by DNA methylation (DNAm) changes. We conducted an EWAS meta-analysis (n=175, 554,979 Illumina EPICv1/EPICv2 sites) in buccal swabs from three hospital-based studies of children with traumatic injuries, stratified by study group to include 1) any traumatic injury, 2) fractures, and 3) traumatic brain injuries. Empirical bayes-moderated linear models tested differential DNAm with M-values, followed ...

ObjectiveSome evidence suggests that higher serum TSH may be a part of normal aging, but current studies are limited to 13-year follow-up. We examined TSH changes during 22 years of follow-up across the adult lifespan. DesignLongitudinal analyses of the population-based HUNT Study in Norway, with TSH measurements from 1995-97, 2006-08 and 2017-19. MethodsIn the overall population and in individuals without thyroid medication or disease, we estimated i) geometric mean serum TSH by age, integrat...

BackgroundLong Interspersed Nucleotide Element-1 (LINE-1, or L1) sequences occupy approximately 17% of the human genome. L1 RNA expression, required for embryogenesis, is low in middle childhood, but increases in adults, eroding heterochromatin and leading to ectopic gene misexpressions, sterile chronic inflammation, and physiological deterioration. To our knowledge, no studies have yet tested whether adults with high L1 RNA levels for their age are shorter-lived, and whether the women with high...

BackgroundPsychosocial adversity (PSA) contributes to long-term health disparities and increased risk for non-communicable diseases. The effects of PSA arise through complex interactions between genes and the environment, which involve immune, endocrine, and epigenetic dysregulation. MethodsTo examine how adversity affects mental and physical health via epigenetic alterations in a more controlled way, we examined the relationship between PSA and epigenetic aging in 28 monozygotic (MZ) twin pair...

Folic acid supplementation during pregnancy is established for preventing neural tube defects, yet its broader neurodevelopmental benefits remain inconsistently observed. Folate receptor autoantibodies (FRAA) may disrupt folate transport, but population evidence is lacking. In a prospective cohort of 3,006 mother-child pairs from the Shanghai Birth Cohort, we precisely quantified maternal red blood cell 5-methyltetrahydrofolate (active folate) and FRAA levels in early pregnancy. We found that hi...

Biological ageing begins before birth, with early-life exposures shaping late-life health. These exposures drive health inequities early, yet specific exposures and the composition of the ageing exposome remain largely undefined. This gap may persist as the field lacks agnostic investigations accounting for non-linearity, interactions and subtle signals. We aimed to identify exposures predictive of epigenetic ageing accumulated during childhood and adolescence and explore the composition of the...

BackgroundMeningioma-induced hyperostosis (MIH) is a frequent radiographic finding, yet its underlying mechanisms remain poorly understoodWhile hyperostosis has traditionally been treated as a binary phenomenon, the aim of this study was to determine whether MIH represents a heterogenous process with distinct radiological subtypes associated with genetic associations. MethodsWe retrospectively reviewed the records and imaging of patients with meningiomas resected between 2021-2024 at a single i...

BackgroundPATZ1 fusion-positive central nervous system (CNS) tumors frequently harbor MN1::PATZ1 fusions as driver mutations, provisionally classified as a rare DNA methylation class of low-grade neuroepithelial tumors. Radiographically, they resemble pilocytic astrocytomas with tumor and cystic components, but their supratentorial cortex location and higher recurrence rates are distinguishing features. An intermediate clinical course, despite focal high-grade histopathology, underscores the nee...

BackgroundMalignant pediatric brain tumors remain the leading cause of cancer-related mortality in children. Current diagnostics rely on imaging and invasive biopsy, which may not capture tumor heterogeneity. Liquid biopsy-based biomarkers such as tumor-educated platelets have shown diagnostic value in adult cancers, but their utility in pediatric brain tumors has not been investigated. MethodsWe analyzed platelet transcriptomes of 73 blood samples from 23 pediatric brain tumor patients, classi...

BackgroundGlioblastoma multiforme (GBM) is an aggressive brain tumor that is notoriously resistant to treatment, with an average survival time of 17 months. While the overall outcome is poor for both males and females, sex differences in GBM incidence and outcome suggest sex-specific biological mechanisms underlie tumorigenesis. In contrast, low-grade glioma (LGG) is a less aggressive brain tumor that tends to have a better prognosis and a longer survival time. MethodsTo understand mechanisms c...

Epigenetic clocks estimate biological age from DNA methylation patterns at CpG sites, providing robust predictions of mortality and morbidity risk. "Blue zones"--regions of exceptional longevity--offer a unique opportunity to investigate how biological aging diverges from chronological age. However, standard clocks are typically trained on large, heterogeneous datasets, reflecting average population trends rather than region-specific dynamics. Using data from the Costa Rican Longevity and Health...

BackgroundMetabolomic changes related to colorectal cancer (CRC) may serve as diagnostic markers to identify patients may develop or have developed CRC. MethodsUntargeted lipidomics were performed on serum from CRC cases and clean-colon controls from the Chicago Colorectal Cancer Consortium (CCCC) and the University of Arizona Cancer Center (UACC). ResultsUntargeted lipidomics in the CCCC CRC series revealed significant alterations in sphingolipids. Targeted lipidomics revealed a signature of ...

Reliable non-invasive biomarkers for tumor grading and disease monitoring in pediatric brain tumors are an unmet clinical need. Circulating extracellular vesicles (EVs) carrying molecular cargo reflective of tumor biology, offer promise as liquid biopsy tools. We have previously discovered EV-associated Syndecan-1 (SDC1) to be overexpressed in malignant brain tumors, but its value as a biomarker in pediatric disease remains unclear. In this study, plasma EVs were isolated from pediatric brain tu...

Importance: Recurrence rates for locally advanced HPV-independent (HPV-) head and neck squamous cell carcinoma (HNSCC) are high. Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assays have shown promise to improve management and surveillance in several tumor types, but their clinical utility in HPV- HNSCC remains understudied. Objective: To evaluate the performance of a tumor-informed ctDNA-based MRD assay (PredicineBEACON) in patients with newly diagnosed, locally advanced H...

Meningiomas are the most common primary brain tumors and, despite their benign reputation, often behave aggressively. Meningiomas are morphologically heterogeneous, yet the full significance of their histologic diversity is unclear. This is in large part because many features are not readily quantifiable by traditional observer-based light microscopy. Molecular testing improves prognostic stratification, but is not universally accessible. We therefore sought to determine whether an artificial in...

IntroductionVery preterm birth (<32 weeks of gestation) disrupts key developmental programs and exposes infants to a highly vulnerable postnatal period. However, the molecular trajectories underlying early postnatal adaptation remain poorly characterized, largely due to limitations in longitudinal sampling and the need for minimally invasive approaches. MethodsHere, we applied an integrated longitudinal proteomic and lipidomic analysis to plasma extracellular vesicles (EVs) from very preterm in...

Much remains unknown about the genetics of immune system changes during pregnancy. We used SNP data in a pregnancy cohort to genetically investigate 47 immune biomarkers at two timepoints, along with change between timepoints (delta). We identified 19 biomarkers with significant SNP-based heritability and 34 with genome-wide significant signals, demonstrating genetic regulation. The same biomarkers measured in early- and mid-pregnancy shared about half of significant associations across timepoin...