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Bias, Conflict of Interest, Ignorance, and Uncertainty
Published in Ted W. Simon, Environmental Risk Assessment, 2019
What some envision is the advent of environment-wide association studies (EWAS), comparable to the genome-wide association studies (GWAS) in genetic epidemiology. Recently, an EWAS revealed a relationship between the metabolic products of the gut flora and cardiovascular disease.125 However, experience with GWASs indicates that careful examination of the results is warranted before using the results for any sort of prognostication.126
The role of epigenetics in the development of childhood asthma
Published in Expert Review of Clinical Immunology, 2019
Cancan Qi, Cheng-Jian Xu, Gerard H. Koppelman
The associations between DNA methylation and diseases can be identified by epigenome-wide association study (EWAS). The global human DNA methylation profile is usually measured by DNA methylation arrays, including the Infinium Human Methylation 450K BeadChip which covers over 450,000 CpGs spread across the whole genome, and the Infinium MethylationEPIC BeadChip which covers around 850,000 CpGs. DNA methylation at a single CpG can be measured by targeted pyrosequencing, which can also be used in validating CpGs identified by EWAS. In EWAS, where hundreds of thousands of CpGs are being evaluated, multiple testing issues should be addressed to reduce false-positive findings. A simple and strict way to adjust for the number of tests is the Bonferroni correction (the significance level is divided by the number of tests), while false discovery rate (FDR) is a more widely used and less conservative method, which controls for the expected ratio of false findings [26].
The current status of blood epigenetic biomarkers for dementia
Published in Critical Reviews in Clinical Laboratory Sciences, 2019
Peter D. Fransquet, Joanne Ryan
Standardization of measurement methods are needed to be able to compare results across studies and cohorts. In the case of DNAm, large-scale epigenome wide association study (EWAS) are preferred over candidate gene studies, although given the expense of these techniques, particularly in large-scale studies, this is a barrier that can be difficult to overcome. With miRNA, concerning both wide scale and candidate studies, a collaborative effort is needed to reach a consensus on a gold standard method for measurement, as one does not currently exist. This would help standardize methodology and ensure proper comparison of findings across studies. Positive and negative controls should always be used and reported to ensure the validity of each study. Detailed analysis techniques should at least be included as supplementary files to allow others to replicate the, at times, complex and multistep analysis.
Identification of diagnostic cytosine-phosphate-guanine biomarkers in patients with gestational diabetes mellitus via epigenome-wide association study and machine learning
Published in Gynecological Endocrinology, 2021
Yan Liu, Zhenglu Wang, Lin Zhao
Epigenetic regulation plays critical roles in various areas, such as methodology, clinical medicine and biomedical applications, and epigenetic markers are implicated in the pathogenesis, prevention and diagnosis of diseases [6]. As expected, epigenetic signatures of GDM may also provide potential biomarkers for its diagnosis, prognosis, and treatment [7]. Moreover, DNA methylation is the most widely studied epigenetic modification in humans, especially the cytosine-phosphate-guanine (CpG) methylation [8]. In normal and diseased cells, this mark is informative for gene regulation, which could potentially act as a biomarker [9]. There are some clues of linking between CpG methylation and GDM. The DNA methylation profiles in placenta demonstrate that CpG methylation aberrancy in GDM is probably associated with the pathophysiology of GDM [10]. Moreover, early pregnancy peripheral blood DNA methylation differences in repeat pregnancies with the change in GDM status [11]. CpG methylation deregulation in adipose tissues and blood cells are associated with gestational diabetes and neonatal outcome [12]. Placental global DNA hypermethylation is also found to be associated with GDM [13]. Thus, DNA methylation as biomarkers may be able to aid the early detection of GDM. However, the specific CpG methylation sites which can be used as the effective biomarkers remain unclear. Epigenome-wide association study (EWAS) is a powerful approach for identification of the epigenetic variations related to biological phenotypes and disease [14]. Although previous research has investigated the function of DNA methylation in GDM via EWAS [15], the identification of GDM based on EWAS is still limited.