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.

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).

Differential Gene Expression in Bladder Tumors from Workers Occupationally Exposed to Arylamines.

Occupational exposure to the arylamines benzidine and -naphthylamine increase bladder cancer risk up to 100-fold, making them some of the most powerful human carcinogens. We hypothesize that tumors arising in people with occupational exposures have different patterns of gene expression than histologically similar tumors from people without such exposures. In a case-case study, we compare gene expression in 22 formalin-fixed paraffin-embedded (FFPE) bladder tumors from men with high-level occupational exposure to arylamines to that in 26 FFPE bladder tumors from men without such exposure.

Blood DNA methylation profiles improve breast cancer prediction.

Although blood DNA methylation (DNAm) profiles are reported to be associated with breast cancer incidence, they have not been widely used in breast cancer risk assessment. Among a breast cancer case-cohort of 2774 women (1551 cases) in the Sister Study, we used candidate CpGs and DNAm estimators of physiologic characteristics to derive a methylation-based breast cancer risk score, mBCRS. Overall, 19 CpGs and five DNAm estimators were selected using elastic net regularization to comprise mBCRS.

Alcohol Consumption and Methylation-Based Measures of Biological Age.

Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with the incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration.

Wavelet Screening identifies regions highly enriched for differentially methylated loci for orofacial clefts.

DNA methylation is the most widely studied epigenetic mark in humans and plays an essential role in normal biological processes as well as in disease development. More focus has recently been placed on understanding functional aspects of methylation, prompting the development of methods to investigate the relationship between heterogeneity in methylation patterns and disease risk. However, most of these methods are limited in that they use simplified models that may rely on arbitrarily chosen parameters, they can only detect differentially methylated regions (DMRs) one at a time, or they are computationally intensive.

Associations of Body Composition and Physical Activity Level With Multiple Measures of Epigenetic Age Acceleration.

Epigenetic clocks use DNA methylation to estimate biological age. Whether body composition and physical activity are associated with these clocks is not well understood. Using blood samples collected at enrollment (2003-2009) from 2,758 women in the US nationwide Sister Study, we calculated 6 epigenetic age acceleration metrics using 4 epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge).

Association of Neighborhood Deprivation With Epigenetic Aging Using 4 Clock Metrics.

Importance: Neighborhood deprivation is associated with age-related disease, mortality, and reduced life expectancy. However, biological pathways underlying these associations are not well understood.

Objective: To evaluate the association between neighborhood deprivation and epigenetic measures of age acceleration and genome-wide methylation.

ipDMR: identification of differentially methylated regions with interval P-values.

Summary: ipDMR is an R software tool for identification of differentially methylated regions (DMRs) using auto-correlated P-values for individual CpGs from epigenome-wide association analysis using array or bisulfite sequencing data. It summarizes P-values for adjacent CpGs, identifies association peaks and then extends peaks to find boundaries of DMRs. ipDMR uses BED format files as input and is easy to use.