Identification of a DNA methylation signature in blood cells from persons with Down Syndrome

Down Syndrome (DS) is characterized by a wide spectrum of clinical signs, which include segmental premature aging of central nervous and immune systems. Although it is well established that the causative defect of DS is the trisomy of chromosome 21, the molecular bases of its phenotype are still largely unknown. We used the Infinium HumanMethylation450 BeadChip to investigate DNA methylation patterns in whole blood from 29 DS persons, using their relatives (mothers and unaffected siblings) as controls. This family-based model allowed us to monitor possible confounding effects on DNA methylation patterns deriving from genetic and environmental factors. Although differentially methylated regions (DMRs) displayed a genome-wide distribution, they were enriched on chromosome 21. DMRs mapped in genes involved in developmental functions, including embryonic development (HOXA family) and haematological (RUNX1 and EBF4) and neuronal (NCAM1) development. Moreover, genes involved in the regulation of chromatin structure (PRMD8, KDM2B, TET1) showed altered methylation. The data also showed that several pathways are affected in DS, including PI3K-Akt signaling. In conclusion, we identified an epigenetic signature of DS that sustains a link between developmental defects and disease phenotype, including segmental premature aging.     

A bibliometric analysis of DNA methylation in cardiovascular diseases from 2001 to 2021

Background:DNA methylation is a dynamically reversible form of epigenetics. Dynamic regulation plays an important role in cardiovascular diseases (CVDs). However, there have been few bibliometric studies in this field. We aimed to visualize the research results and hotspots of DNA methylation in CVDs using a bibliometric analysis to provide a scientific direction for future research.Methods:Publications related to DNA methylation in CVDs from January 1, 2001, to September 15, 2021, were searched and confirmed from the Web of Science Core Collection. CiteSpace 5.7 and VOSviewer 1.6.15 were used for bibliometric and knowledge-map analyses.Results:A total of 2617 publications were included in 912 academic journals by 15,584 authors from 963 institutions from 85 countries/regions. Among them, the United States of America, China, and England were the top 3 countries contributing to the field of DNA methylation. Harvard University, Columbia University, and University of Cambridge were the top 3 contributing institutions in terms of publications and were closely linked. PLoS One was the most published and co-cited journal. Baccarelli Andrea A published the most content, while Barker DJP had the highest frequency of co-citations. The keyword cluster focused on the mechanism, methyl-containing substance, exposure/risk factor, and biomarker. In terms of research hotspots, references with strong bursts, which are still ongoing, recently included “epigenetic clock” (2017–2021), “obesity, smoking, aging, and DNA methylation” (2017–2021), and “biomarker and epigenome-wide association study” (2019–2021).Conclusions:We used bibliometric and visual methods to identify research hotspots and trends in DNA methylation in CVDs. Epigenetic clocks, biomarkers, environmental exposure, and lifestyle may become the focus and frontier of future research.