DNA methylation (DNAm) is one of the most frequently studied epigenetic mechanisms facilitating the interplay of genomic and environmental factors, which can contribute to externalizing behaviours and related psychiatric disorders. Previous epigenome-wide association studies (EWAS) for externalizing behaviours have been limited in sample size, and, therefore, candidate genes and biomarkers with robust evidence are still lacking. We 1) performed a systematic literature review of EWAS of attention-deficit/hyperactivity disorder (ADHD)- and aggression-related behaviours conducted in peripheral tissue and cord blood and 2) combined the most strongly associated DNAm sites observed in individual studies (p < 10-3) to identify candidate genes and biological systems for ADHD and aggressive behaviours. We observed enrichment for neuronal processes and neuronal cell marker genes for ADHD. Astrocyte and granulocytes cell markers among genes annotated to DNAm sites were relevant for both ADHD and aggression-related behaviours. Only 1 % of the most significant epigenetic findings for ADHD/ADHD symptoms were likely to be directly explained by genetic factors involved in ADHD. Finally, we discuss how the field would greatly benefit from larger sample sizes and harmonization of assessment instruments.

UNASSIGNED: Asthma is the most common chronic respiratory disease in the world with an estimated heritability between 50% and 60%, and recent studies have shown that epigenetic mechanisms play an important role in its development. Many cutting-edge epigenetic research techniques have been applied to the study of the pathogenesis of asthma, which has promoted the development of asthma etiology and brought new possibilities for treatment. We summarized recent advances in epigenetic research of the pathogenesis of asthma, especially from the perspective of high-throughput analysis techniques, to find potential epigenetic biomarkers and possible molecular targets for the future intervention and treatment of the disease.
UNASSIGNED: We reviewed and summarized recent progress in epigenomic studies of asthma on a \"pre-transcriptional level\", including DNA methylation, histone modification, and chromatin remodeling, and on a \"post-transcriptional level\" with a focus on non-coding RNA, from the perspective of high-throughput analysis technologies.
UNASSIGNED: We have summarized the progress of different kinds of recent epigenetic studies in asthma, including DNA methylation studies [candidate genes methylation studies and epigenome-wide association study (EWAS)], histone modification studies (histone acetylation/deacetylation studies and histone methylation studies), non-coding RNA studies [microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs)], to help the readers to gain a comprehensive insight into the epigenetic research fields for asthma. The application of high-throughput analysis techniques in asthma research, including EWAS (DNA methylation chips), chromatin immunoprecipitation sequencing (CHIP-seq), microRNA sequencing, whole transcriptome sequencing, co-expression network and competing endogenous RNA (ceRNA) analyses, were introduced accompany with the main findings. And the potential epigenetic biomarkers and possible molecular targets identified via high-throughput analyses were also discussed.
UNASSIGNED: Epigenetic research has become a hotspot in research on the pathogenesis of asthma. The combination of high-throughput epigenetic analysis technologies and traditional biological function and clinical studies will bring new breakthrough in the pathogenesis study of asthma, which will improve the genetic interpretation of the disease and bring more possibilities for the development of precision medicine to treat it.

When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such modifications occur and whether they disrupt normal foetal developme nt, are currently unanswered questions. This field of prenatal pharmacoepigenetics has received increasing attention, with several studies reporting associations between in utero medication exposure and offspring epigenetic outcomes. Nevertheless, no recent systematic review of the literature is available. Therefore, the objectives of this review were to (i) provide an overview of the literature on the association of prenatal exposure to psychotropics a nd analgesics with epigenetic outcomes, and (ii) suggest recommendations for future studies within prenatal pharmacoepigenetics. We performed systematic literature searches in five databases. The eligible studies assessed human prenatal exposure to psychotropics or analgesics, with epigenetic analyses of offspring tissue as an outcome. We identified 18 eligible studies including 4,419 neonates exposed to either antidepressants, antiepileptic drugs, paracetamol, acetylsalicylic acid, or methadone. The epigenetic outcome in all studies was DNA methylation in cord blood, placental tissue or buccal cells. Although most studies found significant differences in DNA methylation upon medication exposure, almost no differences were persistent across studies for similar medications and sequencing methods. The reviewed studies were challenging to compare due to poor transparency in reporting, and heterogeneous methodology, design, genome coverage, and statistical modelling. We propose 10 recommendations for future prenatal pharmacoepigenetic studies considering both epidemiological and epigenetic perspectives. These recommendations may improve the quality, comparability, and clinical relevance of such studies. PROSPERO registration ID: CRD42020166675.

In late 2014, the first epigenome-wide association studies of DNA modifications in Alzheimer\'s disease brain samples were published. Over the last 5 years, further studies have been reported in the field and have highlighted consistent and robust alterations in DNA modifications in AD cortex. However, there are some caveats associated with the majority of studies undertaken to date; for example, they are predominantly restricted to profiling a limited number of loci, are principally focused on DNA methylation, are performed on bulk tissue at the end stage of disease and are restricted to nominating associations rather than demonstrating causal relationships. Consequently, the downstream interpretation of these studies is limited. Owing to recent advances in state-of-the-art cell profiling techniques, long-read genomic technologies and genetic engineering methodologies, identifying cell-type-specific causal epigenetic changes is becoming feasible. This review seeks to provide an overview of the last 5 years of epigenomic studies of DNA modifications in Alzheimer\'s disease brain samples and propose new avenues for future research.

OBJECTIVE: Several studies have investigated the influence of obesity on DNA methylation (DNAm) to find biomarkers associated with the detection of chronic diseases, including breast cancer. The aim of the study was to systematically review studies examining the association of body mass index (BMI) and DNAm in blood or normal breast tissue.
METHODS: Three scientific literature databases (PubMed, Embase and Web of Science) were screened until May 2018.
RESULTS: Twenty-four studies were included along with ours in which we investigated this relation in the normal breast tissue of 40 breast cancer patients.
CONCLUSIONS: BMI-associated CpG sites were highly variable with few identified in less than half of the studies. Nevertheless, a few genes potentially associated with BMI were highlighted in blood (CPT1A, ABCG1, SREBF1 and LGALS3BP) and in normal breast tissue (PTPRN2 and ABLIM2). The variability of the results could be explained by the tissue and cell-specificity of methylation and differences in methodology.

A major challenge faced by epigenome-wide association studies (EWAS) is cell-type heterogeneity. As many EWAS have already demonstrated, adjusting for changes in cell-type composition can be critical when analyzing and interpreting findings from such studies. Because of their importance, a great number of different statistical algorithms, which adjust for cell-type composition, have been proposed. Some of the methods are \'reference based\' in that they require a priori defined reference DNA methylation profiles of cell types that are present in the tissue of interest, while other algorithms are \'reference free.\' At present, however, it is unclear how best to adjust for cell-type heterogeneity, as this may also largely depend on the type of tissue and phenotype being considered. Here, we provide a critical review of the major existing algorithms for correcting cell-type composition in the context of Illumina Infinium Methylation Beadarrays, with the aim of providing useful recommendations to the EWAS community.