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Biology
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DNA Methylation and Epigenetics 2.0
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DNA Methylation and Epigenetics 2.0

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Genetics and Genomics".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 7113

Special Issue Editor

Dr. Giovanni Fiorito

E-Mail Website
Guest Editor
Clinical Bioinformatics Unit, IRCCS Istituto Giannina Gaslini, 5-16147 Genova, Italy
Interests: bioinformatics; machine learning; epigenetics; molecular epidemiology; DNA methylation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent studies highlight the epidemiological value of DNA methylation (DNAm) as a robust biomarker for healthy ageing and exposure to risk factors, with the possibility of identifying signatures for noncommunicable and age-related diseases, including cancer, cardiovascular diseases, and mental disorders.

Besides recently developed epigenetic clocks, DNAm has been successfully used as a surrogate biomarker for different exposures, showing that, in some cases, DNAm surrogates predict diseases better than the measured risk factors themselves. DNAm characteristics can explain these counterintuitive results:

  1. In many cases, DNAm is a more reliable biomarker than self-reported or measured exposures (e.g., for smoking).
  2. DNAm variability includes individual genetic and metabolic profiles that can influence individual responses to exposure and stressors (i.e., the same amount of exposure can be more or less dangerous based on genetic profile and general state of health).
  3. DNAm variations reflect long-term exposures and are more stable in time than other volatile biomarkers (e.g., blood-measured proteins and hormones).

Further investigations in this field may help us identify diagnostic and prognostic disease biomarkers (hopefully noninvasively by using blood/urine/saliva samples), molecular mechanisms responsible for the development of cancer, cardiovascular diseases, and mental diseases, as well as possible therapeutic targets.

Dr. Giovanni Fiorito
Guest Editor

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Keywords

  • epigenetics
  • DNA methylation
  • DNAm surrogates
  • diagnostic biomarkers
  • prognostic biomarkers
  • age-related diseases
  • therapeutic targets

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Published Papers (3 papers)

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10 pages, 1739 KiB  
Communication
Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study
by Biying Lin, Yuzhu Mu and Zhongxiang Ding
Biology 2023, 12(5), 660; https://doi.org/10.3390/biology12050660 - 27 Apr 2023
Cited by 1 | Viewed by 2608
Abstract
Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers [...] Read more.
Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers in the development of CSVD. We performed a Mendelian randomization (MR) study of LTL and four epigenetic clocks on ten subclinical and clinical CSVD measures. We obtained genome-wide association (GWAS) data for LTL from the UK Biobank (N = 472,174). Data on epigenetic clocks were derived from a meta-analysis (N = 34,710), and CSVD data (N cases =1293–18,381; N controls = 25,806–105,974) were extracted from the Cerebrovascular Disease Knowledge Portal. We found that genetically determined LTL and epigenetic clocks were not individually associated with ten measures of CSVD (IVW p > 0.05), and this result was consistent across sensitivity analyses. Our findings imply that LTL and epigenetic clocks may not help in predicting CSVD development as causal prognostic biomarkers. Further studies are needed to illustrate the potential of reverse biological aging in serving as an effective form of preventive therapy for CSVD. Full article
(This article belongs to the Special Issue DNA Methylation and Epigenetics 2.0)
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18 pages, 2211 KiB  
Article
Inter-Individual Variation in DNA Methylation Patterns across Two Tissues and Leukocytes in Mature Brahman Cattle
by Emilie C. Baker, Audrey E. San, Kubra Z. Cilkiz, Brittni P. Littlejohn, Rodolfo C. Cardoso, Noushin Ghaffari, Charles R. Long, Penny K. Riggs, Ronald D. Randel, Thomas H. Welsh, Jr. and David G. Riley
Biology 2023, 12(2), 252; https://doi.org/10.3390/biology12020252 - 5 Feb 2023
Cited by 1 | Viewed by 1772
Abstract
Quantifying the natural inter-individual variation in DNA methylation patterns is important for identifying its contribution to phenotypic variation, but also for understanding how the environment affects variability, and for incorporation into statistical analyses. The inter-individual variation in DNA methylation patterns in female cattle [...] Read more.
Quantifying the natural inter-individual variation in DNA methylation patterns is important for identifying its contribution to phenotypic variation, but also for understanding how the environment affects variability, and for incorporation into statistical analyses. The inter-individual variation in DNA methylation patterns in female cattle and the effect that a prenatal stressor has on such variability have yet to be quantified. Thus, the objective of this study was to utilize methylation data from mature Brahman females to quantify the inter-individual variation in DNA methylation. Pregnant Brahman cows were transported for 2 h durations at days 60 ± 5; 80 ± 5; 100 ± 5; 120 ± 5; and 140 ± 5 of gestation. A non-transport group was maintained as a control. Leukocytes, amygdala, and anterior pituitary glands were harvested from eight cows born from the non-transport group (Control) and six from the transport group (PNS) at 5 years of age. The DNA harvested from the anterior pituitary contained the greatest variability in DNA methylation of cytosine-phosphate-guanine (mCpG) sites from both the PNS and Control groups, and the amygdala had the least. Numerous variable mCpG sites were associated with retrotransposable elements and highly repetitive regions of the genome. Some of the genomic features that had high variation in DNA methylation are involved in immune responses, signaling, responses to stimuli, and metabolic processes. The small overlap of highly variable CpG sites and features between tissues and leukocytes supports the role of variable DNA methylation in regulating tissue-specific gene expression. Many of the CpG sites that exhibited high variability in DNA methylation were common between the PNS and Control groups within a tissue, but there was little overlap in genomic features with high variability. The interaction between the prenatal environment and the genome could be responsible for the differences in location of the variable DNA methylation. Full article
(This article belongs to the Special Issue DNA Methylation and Epigenetics 2.0)
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11 pages, 778 KiB  
Systematic Review
HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review
by Marjanu Hikmah Elias, Nurunnajah Lazim, Zulazmi Sutaji, Mohammad Azrai Abu, Abdul Kadir Abdul Karim, Azizah Ugusman, Saiful Effendi Syafruddin, Mohd Helmy Mokhtar and Mohd Faizal Ahmad
Biology 2023, 12(3), 474; https://doi.org/10.3390/biology12030474 - 20 Mar 2023
Cited by 4 | Viewed by 2195
Abstract
Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve [...] Read more.
Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR “homeobox A10” OR “HOXA-10” OR HOX1) AND (“DNA methylation” OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis. Full article
(This article belongs to the Special Issue DNA Methylation and Epigenetics 2.0)
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