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Clinical Epigenetics May 2024DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid...
OBJECTIVE
DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid early detection and/or therapeutic treatment options for diabetics.
DESIGN
A systematic literature search for associations between T2DM and DNA methylation was performed. Prospero registration ID: CRD42020140436.
METHODS
PubMed and ScienceDirect databases were searched (till October 19, 2023). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and New Castle Ottawa scale were used for reporting the selection and quality of the studies, respectively.
RESULT
Thirty-two articles were selected. Four of 130 differentially methylated genes in blood, adipose, liver or pancreatic islets (TXNIP, ABCG1, PPARGC1A, PTPRN2) were reported in > 1 study. TXNIP was hypomethylated in diabetic blood across ethnicities. Gene enrichment analysis of the differentially methylated genes highlighted relevant disease pathways (T2DM, type 1 diabetes and adipocytokine signaling). Three prospective studies reported association of methylation in IGFBP2, MSI2, FTO, TXNIP, SREBF1, PHOSPHO1, SOCS3 and ABCG1 in blood at baseline with incident T2DM/hyperglycemia. Sex-specific differential methylation was reported only for HOOK2 in visceral adipose tissue (female diabetics: hypermethylated, male diabetics: hypomethylated). Gene expression was inversely associated with methylation status in 8 studies, in genes including ABCG1 (blood), S100A4 (adipose tissue), PER2 (pancreatic islets), PDGFA (liver) and PPARGC1A (skeletal muscle).
CONCLUSION
This review summarizes available evidence for using DNA methylation patterns to unravel T2DM pathophysiology. Further validation studies in diverse populations will set the stage for utilizing this knowledge for identifying early diagnostic markers and novel druggable pathways.
Topics: Female; Humans; Male; Carrier Proteins; Diabetes Mellitus, Type 2; DNA Methylation; Epigenesis, Genetic
PubMed: 38755631
DOI: 10.1186/s13148-024-01670-6 -
Neuroscience and Biobehavioral Reviews Apr 2023Child maltreatment (CM) encompasses sexual abuse, physical abuse, emotional abuse, neglect, and exposure to domestic and family violence. Epigenetic research... (Review)
Review
Child maltreatment (CM) encompasses sexual abuse, physical abuse, emotional abuse, neglect, and exposure to domestic and family violence. Epigenetic research investigating CM has focused on differential DNA methylation (DNAm) in genes associated with the stress response, but there has been limited evaluation of the specific effects of subtypes of CM. This systematic review of literature investigating DNAm associated with CM in non-clinical populations aimed to summarise the approaches currently used in research, how the type of maltreatment and age of exposure were encoded via methylation, and which genes have consistently been associated with CM. A total of fifty-four papers were eligible for review, including forty-one candidate gene studies, eight epigenome-wide association studies, and five studies with a mixed design. The ways in which the various forms of CM were conceptualised and measured varied between papers. Future studies would benefit from assessments that employ conceptually robust definitions of CM, and that capture important contextual information such as age of exposure and subtype of CM.
Topics: Child; Humans; DNA Methylation; Child Abuse
PubMed: 36764637
DOI: 10.1016/j.neubiorev.2023.105079 -
Neuroscience and Biobehavioral Reviews Jun 2020MRI has enhanced our capacity to understand variations in brain structure and function conferred by the genome. We identified 60 studies that report associations between... (Review)
Review
MRI has enhanced our capacity to understand variations in brain structure and function conferred by the genome. We identified 60 studies that report associations between DNA methylation (DNAm) and human brain structure/function. Forty-three studies measured candidate loci DNAm; seventeen measured epigenome-wide DNAm. MRI features included region-of-interest and whole-brain structural, diffusion and functional imaging features. The studies report DNAm-MRI associations for: neurodevelopment and neurodevelopmental disorders; major depression and suicidality; alcohol use disorder; schizophrenia and psychosis; ageing, stroke, ataxia and neurodegeneration; post-traumatic stress disorder; and socio-emotional processing. Consistency between MRI features and differential DNAm is modest. Sources of bias: variable inclusion of comparator groups; different surrogate tissues used; variation in DNAm measurement methods; lack of control for genotype and cell-type composition; and variations in image processing. Knowledge of MRI features associated with differential DNAm may improve understanding of the role of DNAm in brain health and disease, but caution is required because conventions for linking DNAm and MRI data are not established, and clinical and methodological heterogeneity in existing literature is substantial.
Topics: Brain; DNA Methylation; Emotions; Epigenesis, Genetic; Epigenome; Genotype; Humans
PubMed: 32151655
DOI: 10.1016/j.neubiorev.2020.03.007 -
International Journal of Molecular... Apr 2023This systematic review and meta-analysis summarize the difference in the methylation of the gene in patients with abnormal versus normal conventional sperm parameters.... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis summarize the difference in the methylation of the gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.
Topics: Female; Humans; Male; Pregnancy; DNA Methylation; Genomic Imprinting; Histones; Infertility, Male; Meta-Analysis as Topic; Semen; Spermatozoa
PubMed: 37108386
DOI: 10.3390/ijms24087224 -
Clinical Epigenetics Sep 2023Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have long-lasting detrimental consequences for the mental health of the offspring later in life. One epigenetic mechanism that has been associated with mental disorders and undernutrition is alterations in DNA methylation. The effect of prenatal undernutrition on the mental health of adult offspring can be analyzed through quasi-experimental studies such as famine studies. The present systematic review and meta-analysis aims to analyze the association between prenatal famine exposure, DNA methylation, and mental disorders in adult offspring. We further investigate whether altered DNA methylation as a result of prenatal famine exposure is prospectively linked to mental disorders.
METHODS
We conducted a systematic search of the databases PubMed and PsycINFO to identify relevant records up to September 2022 on offspring whose mothers experienced famine directly before and/or during pregnancy, examining the impact of prenatal famine exposure on the offspring's DNA methylation and/or mental disorders or symptoms.
RESULTS
The systematic review showed that adults who were prenatally exposed to famine had an increased risk of schizophrenia and depression. Several studies reported an association between prenatal famine exposure and hyper- or hypomethylation of specific genes. The largest number of studies reported differences in DNA methylation of the IGF2 gene. Altered DNA methylation of the DUSP22 gene mediated the association between prenatal famine exposure and schizophrenia in adult offspring. Meta-analysis confirmed the increased risk of schizophrenia following prenatal famine exposure. For DNA methylation, meta-analysis was not suitable due to different microarrays/data processing approaches and/or unavailable data.
CONCLUSION
Prenatal famine exposure is associated with an increased risk of mental disorders and DNA methylation changes. The findings suggest that changes in DNA methylation of genes involved in neuronal, neuroendocrine, and immune processes may be a mechanism that promotes the development of mental disorders such as schizophrenia and depression in adult offspring. Such findings are crucial given that undernutrition has risen worldwide, increasing the risk of famine and thus also of negative effects on mental health.
Topics: Pregnancy; Adult; Female; Humans; DNA Methylation; Famine; Mental Disorders; Vitamins; Malnutrition
PubMed: 37716973
DOI: 10.1186/s13148-023-01557-y -
Translational Psychiatry Feb 2021Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis... (Review)
Review
Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis that maltreatment is associated with epigenetic changes that may subsequently serve as mechanisms of disease. The current review uses a systematic approach to identify and summarize the literature related to childhood maltreatment and alterations in DNA methylation in humans. A total of 100 empirical articles were identified in our systematic review of research published prior to or during March 2020, including studies that focused on candidate genes and studies that leveraged epigenome-wide data in both children and adults. Themes arising from the literature, including consistent and inconsistent patterns of results, are presented. Several directions for future research, including important methodological considerations for future study design, are discussed. Taken together, the literature on childhood maltreatment and DNA methylation underscores the complexity of transactions between the environment and biology across development.
Topics: Adult; Child; Child Abuse; DNA Methylation; Epigenesis, Genetic; Epigenome; Humans; Risk Factors
PubMed: 33608499
DOI: 10.1038/s41398-021-01207-y -
Psychiatry Research Jan 2022Schizophrenia has a large disease burden globally. Early intervention in psychosis, and therefore a decreased duration of untreated psychosis, has a positive clinical... (Review)
Review
BACKGROUND
Schizophrenia has a large disease burden globally. Early intervention in psychosis, and therefore a decreased duration of untreated psychosis, has a positive clinical impact. There are several recognized risk factors for psychosis, including trauma history and substance use. This systematic review examined the literature for studies related to epigenetic changes in first-episode psychosis, with the goal of identifying future research directions.
METHODS
A literature review was conducted from inception to October 3, 2021 using MedLine/PubMed, Web of Science, and PsycInfo searches with the keywords ("first-episode schizophrenia" OR "first-episode psychosis" OR "drug-naive schizophrenia" OR "drug-naive psychosis") AND (epigenetic OR methylation OR hydroxymethylation OR "histone modification" OR "miRNA") as well as a search of the bibliography of the identified papers.
RESULTS
Seventeen studies that examined various portions of the genome were included in this systematic review. There were two studies that showed hypomethylation at the LINE-1 portion of the genome and two that showed hypermethylation at LINE-1. Additionally, two studies showed hypomethylation specifically at the GRIN2B promoter (part of LINE-1).
CONCLUSIONS
Although sample sizes were small, these studies provide evidence for epigenetic alterations in early psychosis. Further research in this area is warranted for more definitive epigenetic correlations.
Topics: DNA Methylation; Epigenesis, Genetic; Humans; Promoter Regions, Genetic; Psychotic Disorders; Schizophrenia
PubMed: 34896847
DOI: 10.1016/j.psychres.2021.114325 -
EBioMedicine May 2024This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective.
METHODS
Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations. In epigenetic two-sample Mendelian randomization analyses, we examine the associations between genetically predicted DNA methylation related to air pollution and CRC risk. Further genetic colocalization and gene-environment interaction analyses provided different insights to disentangle pathogenic effects of air pollution via epigenetic modification.
FINDINGS
During a median 12.97-year follow-up, 5767 incident CRC cases among 428,632 participants free of baseline CRC and 533 deaths in 2401 patients with CRC were documented in the UK Biobank. A higher APES score was associated with an increased CRC risk (HR, 1.03, 95% CI = 1.01-1.06; P = 0.016) and poorer survival (HR, 1.13, 95% CI = 1.03-1.23; P = 0.010), particularly among participants with insufficient physical activity and ever smokers (P > 0.05). A subsequent meta-analysis of seven observational studies, including UK Biobank data, corroborated the association between PM exposure (per 10 μg/m increment) and elevated CRC risk (RR,1.42, 95% CI = 1.12-1.79; P = 0.004; I = 90.8%). Genetically predicted methylation at PM-related CpG site cg13835894 near TMBIM1/PNKD and cg16235962 near CXCR5, and NO-related cg16947394 near TMEM110 were associated with an increased CRC risk. Gene-environment interaction analysis confirmed the epigenetic modification of aforementioned CpG sites with CRC risk and survival.
INTERPRETATION
Our study suggests the association between air pollution and CRC incidence and survival, underscoring the possible modifying roles of epigenomic factors. Methylation may partly mediate pathogenic effects of air pollution on CRC, with annotation to epigenetic alterations in protein-coding genes TMBIM1/PNKD, CXCR5 and TMEM110.
FUNDING
Xue Li is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), the National Nature Science Foundation of China (No. 82204019) and Healthy Zhejiang One Million People Cohort (K-20230085). ET is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804). MGD is supported by the MRC Human Genetics Unit Centre Grant (U127527198).
Topics: Aged; Female; Humans; Male; Middle Aged; Air Pollutants; Air Pollution; Colorectal Neoplasms; DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Epigenomics; Gene-Environment Interaction; Incidence; Mendelian Randomization Analysis; Prospective Studies; Risk Factors
PubMed: 38631091
DOI: 10.1016/j.ebiom.2024.105126 -
Wiley Interdisciplinary Reviews. RNA Nov 2021In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding... (Review)
Review
In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA-dependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N-MTase activity of EZH2, protein arginine-MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
Topics: Animals; Gene Expression Regulation; Methylation; Protein Processing, Post-Translational; RNA Processing, Post-Transcriptional; RNA, Long Noncoding
PubMed: 33913612
DOI: 10.1002/wrna.1661 -
International Journal of Molecular... May 2023Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, the underlying pathological mechanisms of which are not yet completely understood. Although... (Review)
Review
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, the underlying pathological mechanisms of which are not yet completely understood. Although several genetic and genomic alterations have been linked to ASD, for the majority of ASD patients, the cause remains unknown, and the condition likely arises due to complex interactions between low-risk genes and environmental factors. There is increasing evidence that epigenetic mechanisms that are highly sensitive to environmental factors and influence gene function without altering the DNA sequence, particularly aberrant DNA methylation, are involved in ASD pathogenesis. This systematic review aimed to update the clinical application of DNA methylation investigations in children with idiopathic ASD, investigating its potential application in clinical settings. To this end, a literature search was performed on different scientific databases using a combination of terms related to the association between peripheral DNA methylation and young children with idiopathic ASD; this search led to the identification of 18 articles. In the selected studies, DNA methylation is investigated in peripheral blood or saliva samples, at both gene-specific and genome-wide levels. The results obtained suggest that peripheral DNA methylation could represent a promising methodology in ASD biomarker research, although further studies are needed to develop DNA-methylation-based clinical applications.
Topics: Humans; Child; Child, Preschool; DNA Methylation; Autism Spectrum Disorder; Epigenesis, Genetic; Biomarkers; Phenotype
PubMed: 37298088
DOI: 10.3390/ijms24119138