DNA methylation-based health predictors: advances, applications, and perspectives.

DNA methylation (DNAm) has emerged as a powerful and dynamic biomarker for predicting health outcomes, biological aging, and disease risk. Unlike static genetic variants, DNAm is dynamic and influenced by environmental, lifestyle, and pathological factors, making it highly suitable for applications in personalized medicine. This review provides a comprehensive synthesis of recent advances in DNAm-based predictors, including epigenetic clocks, exposure biomarkers, disease risk models, and trait-specific estimators.

Efficient gene set analysis for DNA methylation addressing probe dependency and bias.

Motivation: Gene Set Enrichment Analysis (GSEA) is widely used to interpret DNA methylation data by associating differentially methylated sites with biological pathways. However, existing GSEA methods struggle with several challenges in methylation data, including probe dependency, probe number bias, and the complexity of gene-probe mapping. These limitations can lead to biased enrichment results, reduced statistical power, and computational inefficiencies.

Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood.

Background: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear.

Objective: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e.

Association Between Body Iron Status and Biological Aging.

Background/objectives: Iron is necessary for bodily function, but abnormal levels can increase the risk of chronic diseases. Studies of leukocyte telomere length suggest blood iron levels are positively associated with cellular senescence and accelerated aging. However, associations between blood iron and more robust metrics of biological aging, specifically those based on DNA methylation, have not been examined.

Early life trauma patterns and adult epigenome-wide and NR3C1-specific DNA methylation in the Sister Study.

Patterns of co-occurring early life trauma (ELT), unlike cumulative trauma, are understudied as potential stress-related health risks. DNA methylation (DNAm) is a posited mechanism linking socioenvironmental stress and disease pathogenesis. We assess whether ELT patterns differentially affect adult DNAm, both epigenome-wide and specifically stress-related genes (e.

Calcium signals shape metabolic control of H3K27ac and H3K18la to regulate EGA.

The use of assisted reproductive technologies (ART) has enabled the birth of over 9 million babies; but it is associated with increased risks of negative metabolic outcomes in offspring. Yet, the underlying mechanism remains unknown. Calcium (Ca) signals, which initiate embryo development at fertilization, are frequently disrupted in human ART.

DNA methylation-predicted plasma protein levels and breast cancer risk.

Background: Blood DNA methylation (DNAm) profiles have been used to show that changes in circulating leukocyte composition occur during breast cancer development, suggesting that peripheral immune system alterations are markers of breast cancer risk. Blood DNAm profiles have recently been used to predict plasma protein concentrations ("Protein EpiScores"), but their associations with breast cancer risk have not been examined in detail.

Methods: Whole blood DNAm profiles were obtained for a case-cohort sample of participants in the Sister Study and used to calculate 109 Protein EpiScores.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

The association between toenail metals and extracellular MicroRNAs (ex-miRNAs) among the participants of the Normative Aging study (NAS).

Background: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression.

Methods: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses.

Associations between use of chemical hair products and epigenetic age: Findings from the Sister Study.

Background: Hair products may be a source of harmful chemicals and have been linked to age-related health outcomes. We investigated whether the use of hair products is related to epigenetic age in a sample of Black (both Hispanic and non-Hispanic) and non-Hispanic White women.

Methods: In a subset of 4358 participants aged 35-74 years from the Sister Study, we estimated cross-sectional associations between self-reported use of four chemical hair products (permanent dye, semipermanent dye, straighteners/relaxers, and hair permanents/body waves) in the year before enrollment (2003-2009) and three DNA methylation-based measures of epigenetic age (DunedinPACE, GrimAge age acceleration [GrimAgeAccel], and PhenoAge age acceleration [PhenoAgeAccel]) using survey-weighted multivariable linear regressions.

methscore: a comprehensive R function for DNA methylation-based health predictors.

Motivation: DNA methylation-based predictors of various biological metrics have been widely published and are becoming valuable tools in epidemiologic studies of epigenetics and personalized medicine. However, generating these predictors from original source software and web servers is complex and time consuming. Furthermore, different predictors were often derived based on data from different types of arrays, where array differences and batch effects can make predictors difficult to compare across studies.

Circulating Leukocyte Subsets Before and After a Breast Cancer Diagnosis and Therapy.

Importance: Changes in leukocyte composition often precede chronic disease onset. Patients with a history of breast cancer (hereinafter referred to as breast cancer survivors) are at increased risk for subsequent chronic diseases, but the long-term changes in peripheral leukocyte composition following a breast cancer diagnosis and treatment remain unknown.

Objective: To examine longitudinal changes in peripheral leukocyte composition in women who did and did not develop breast cancer and identify whether differences in breast cancer survivors were associated with specific treatments.

Air pollution and epigenetic aging among Black and White women in the US.

Background: DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women.

Objective: We examined associations of ambient particulate matter <2.

Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study.

Background: Epigenome-wide association studies of ambient fine particulate matter (PM) have been reported. However, few have examined PM components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation.

Changes in methylation-based aging in women who do and do not develop breast cancer.

Background: Breast cancer survivors have increased incidence of age-related diseases, suggesting that some survivors may experience faster biological aging.

Methods: Among 417 women enrolled in the prospective Sister Study cohort, DNA methylation data were generated on paired blood samples collected an average of 7.7 years apart and used to calculate 3 epigenetic metrics of biological aging (PhenoAgeAccel, GrimAgeAccel, and Dunedin Pace of Aging Calculated from the Epigenome [DunedinPACE]).

In utero exposure to diethylstilbestrol and blood DNA methylation in adult women: Results from a meta-analysis of two cohort studies.

Background: Prenatal exposure to diethylstilbestrol (DES) is associated with several adverse health outcomes. Animal studies have shown associations between prenatal DES exposure and DNA methylation.

Objective: The aim of this study was to explore blood DNA methylation in women exposed and unexposed to DES in utero.

Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS).

Background: The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.

Objectives: To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.

Methods: Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015.

Accelerated epigenetic aging and myopenia in young adult cancer survivors.

Background: Young adult cancer survivors experience early aging-related morbidities and mortality. Biological aging biomarkers may identify at-risk survivors and increase our understanding of mechanisms underlying this accelerated aging.

Methods: Using an observational study design, we cross-sectionally measured DNA methylation-based epigenetic age in young adult cancer survivors at a tertiary, academic state cancer hospital.

Beadchip technology to detect DNA methylation in mouse faithfully recapitulates whole-genome bisulfite sequencing.

To facilitate wide-scale implementation of Illumina Mouse Methylation BeadChip (MMB) technology, array-based measurement of cytosine methylation was compared with the gold-standard assessment of DNA methylation by whole-genome bisulfite sequencing (WGBS). DNA methylation across two mouse strains (C57B6 and C3H) and both sexes was assessed using the MMB and compared with previously existing deep-coverage WGBS of mice of the same strain and sex. The findings demonstrated that 93.

Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants.

Background: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.

Methods: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015.

Epigenome-wide DNA methylation in leukocytes and toenail metals: The normative aging study.

Background: Environmental metal exposures have been associated with multiple deleterious health endpoints. DNA methylation (DNAm) may provide insight into the mechanisms underlying these relationships. Toenail metals are non-invasive biomarkers, reflecting a medium-term time exposure window.

Peripheral Immune Cell Composition is Altered in Women Before and After a Hypertension Diagnosis.

Background: The development and consequences of hypertension involve multiple biological systems that may include changes in immune profiles. Whether hypertension is related to peripheral immune cell composition has not been examined in large human cohorts.

Methods: We estimated circulating proportions of 12 leukocyte subsets from the lymphoid and myeloid lineages by deconvolving cell-type-specific DNA methylation data from 4124 women.

Clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in liver.

Objectives: To explore the clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in the liver and investigate the association between such small nodular lesions and the degree of tumor differentiation.

Methods: Combined imaging modalities were performed on 120 patients who were admitted by Linyi Maternal and Child Health hospital from December 2018 to December 2020 and diagnosed with hepatic nodular lesions. The CT scans were interpreted by two senior imageologists while the ultrasound scans were analyzed by two senior sonographers.

The ENmix DNA methylation analysis pipeline for Illumina BeadChip and comparisons with seven other preprocessing pipelines.

Background: Illumina DNA methylation arrays are high-throughput platforms for cost-effective genome-wide profiling of individual CpGs. Experimental and technical factors introduce appreciable measurement variation, some of which can be mitigated by careful "preprocessing" of raw data.

Methods: Here we describe the ENmix preprocessing pipeline and compare it to a set of seven published alternative pipelines (ChAMP, Illumina, SWAN, Funnorm, Noob, wateRmelon, and RnBeads).