Multiple studies have related psychiatric disorders and immune alterations. Panic disorder (PD) has been linked with changes in leukocytes distributions in several small studies using different methods for immune characterization. Additionally, alterations in the methylation of repetitive DNA elements, such as LINE-1, have been associated with mental disorders. Here, we use peripheral blood DNA methylation data from two studies and an updated DNA methylation deconvolution library to investigate the relation of leukocyte proportions and methylation status of repetitive elements in 133 patients with panic disorder compared with 118 controls.

Among men, prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer death. Etiologic factors associated with both prostate carcinogenesis and somatic alterations in tumors are incompletely understood. While genetic variants associated with PCa have been identified, epigenetic alterations in PCa are relatively understudied. To date, DNA methylation (DNAm) and gene expression (GE) in PCa have been investigated; however, these studies did not correct for cell-type proportions of the tumor microenvironment (TME), which could confound results.

Differentially methylated regions (DMRs) within DNA isolated from whole blood can be used to estimate the proportions of circulating leukocyte subtypes. We use the term "immunomethylomics" to describe the application of these immune lineage DMRs to studying leukocyte profiles. Here, we applied this approach to peripheral blood DNA from 72 glioma patients with molecularly defined brain tumors, representing common patient groups with defined characteristic survival times and risk factors. We first estimated the proportions of leukocyte subtypes in samples using deconvolution algorithms with reference DMR libraries from isolated leukocyte populations and Illumina 450K DNA methylation data. Then, we calculated the neutrophil to lymphocyte ratio (NLR) using methylation-derived cell composition estimates (mdNLR). The NLR is considered an indicator of immunosuppressive cells in cancer patients.

Epigenetic mechanisms are thought to be critical in mediating the role of the intrauterine environment on lifelong health and disease. Twin-twin transfusion syndrome (TTTS) is a rare condition wherein fetuses share the placenta and develop vascular anastomoses, which allow blood to flow between the fetuses. The unequal flow results in reciprocal hypo- and hypervolemia in the affected twins, striking growth differences and physiologic adaptations in response to this significant stressor. The donor twin in the TTTS syndrome can be profoundly growth restricted and there is likely a nutritional imbalance between the twins. The consequences of TTTS on fetal programming are unknown. This condition can now be effectively treated through the use of fetal laparoscopic procedures, but the potential for lifelong morbidity related to this condition during development is apparent. As this condition and the resulting uteroplacental discordance can play a role in the epigenetic process, we sought to investigate the DNA methylation profiles of childhood survivors of TTTS (n = 14). We focused on differences in both global measures and genome-wide CpG specific DNA methylation between donor and recipient children in this pilot study in order to generate hypotheses for further research.

Nucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system (CNS) tumors. 5hmC is abundant in the brain, and alterations to 5hmC in adult CNS tumors have been reported. However, traditional approaches to measure DNA methylation do not distinguish between 5-methylcytosine (5mC) and its oxidized counterpart 5hmC, including those used to build CNS tumor DNA methylation classification systems. We measured 5hmC and 5mC epigenome-wide at nucleotide resolution in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using tandem bisulfite and oxidative bisulfite treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG loci.

Lung macrophages are major participants in the pulmonary innate immune response. In the cystic fibrosis (CF) lung, the inability of lung macrophages to successfully regulate the exaggerated inflammatory response suggests dysfunctional innate immune cell function. In this study, we aim to gain insight into innate immune cell dysfunction in CF by investigating alterations in DNA methylation in bronchoalveolar lavage (BAL) cells, composed primarily of lung macrophages of CF subjects compared with healthy controls. All analyses were performed using primary alveolar macrophages from human subjects collected via bronchoalveolar lavage. Epigenome-wide DNA methylation was examined via Illumina MethylationEPIC (850 K) array. Targeted next-generation bisulfite sequencing was used to validate selected differentially methylated CpGs. Methylation-based sample classification was performed using the recursively partitioned mixture model (RPMM) and was tested against sample case-control status. Differentially methylated loci were identified by fitting linear models with adjustment of age, sex, estimated cell type proportions, and repeat measurement.

Umbilical cord blood (UCB) is commonly used in epigenome-wide association studies of prenatal exposures. Accounting for cell type composition is critical in such studies as it reduces confounding due to the cell specificity of DNA methylation (DNAm). In the absence of cell sorting information, statistical methods can be applied to deconvolve heterogeneous cell mixtures. Among these methods, reference-based approaches leverage age-appropriate cell-specific DNAm profiles to estimate cellular composition. In UCB, four reference datasets comprising DNAm signatures profiled in purified cell populations have been published using the Illumina 450 K and EPIC arrays. These datasets are biologically and technically different, and currently, there is no consensus on how to best apply them. Here, we systematically evaluate and compare these datasets and provide recommendations for reference-based UCB deconvolution.

Assessing functional ability is an important component of understanding healthy aging. Objective measures of functional ability include grip strength, gait speed, sit-to-stand time, and 6-min walk distance. Using samples from a weight loss clinical trial in older adults with obesity, we examined the association between changes in physical function and DNA-methylation-based biological age at baseline and 12 weeks in 16 individuals. Peripheral blood DNA methylation was measured (pre/post) with the Illumina HumanMethylationEPIC array and the Hannum, Horvath, and PhenoAge DNA methylation age clocks were used. Linear regression models adjusted for chronological age and sex tested the relationship between DNA methylation age and grip strength, gait speed, sit-to-stand, and 6-min walk.

Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive lesion associated with an increased risk for future invasive ductal carcinoma. However, accurate risk stratification for development of invasive disease and appropriate treatment decisions remain clinical challenges. DNA methylation alterations are early events in the progression of cancer and represent emerging molecular markers that may predict invasive recurrence more accurately than traditional measures of DCIS prognosis.

Myeloid-derived suppressor cells (MDSCs), which include monocytic (mMDSCs) and granulocytic (gMDSCs) cells, are an immunosuppressive, heterogeneous population of cells upregulated in cancer and other pathologic conditions, in addition to normal conditions of stress. The origin of MDSCs is debated, and the regulatory pattern responsible for gMDSC differentiation remains unknown. Since DNA methylation (DNAm) contributes to lineage differentiation, we have investigated whether it contributes to the acquisition of the gMDSC phenotype.