scholarly journals DNA Methylation Signature in Monozygotic Twins Discordant for Psoriatic Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Matteo Vecellio ◽  
Elvezia Maria Paraboschi ◽  
Angela Ceribelli ◽  
Natasa Isailovic ◽  
Francesca Motta ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Responses ◽  
Monozygotic Twins ◽  
Disease Status ◽  
Monozygotic Twin ◽  
Joint Involvement ◽  
Transcriptome Data ◽  
Psoriatic Disease ◽  
Altered Glucose ◽  
A Genome

Background: Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics.Methods: We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP—qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs.Results: We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δβ-values (p < 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-β signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-α pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients’ immune cells, characteristic of pro-inflammatory T lymphocytes.Conclusion: The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

T.N.3 A GENOME-WIDE DNA METHYLATION STUDY IN MONOZYGOTIC TWINS DISCORDANT FOR PRIMARY BILIARY CIRRHOSIS

2010 ◽  
Vol 42 ◽  
pp. S16
Author(s):  
A. Lleo ◽  
M.R. Martin ◽  
L. Zammataro ◽  
M.J. Mayo ◽  
N. Bach ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Primary Biliary Cirrhosis ◽  
Monozygotic Twins ◽  
Biliary Cirrhosis ◽  
Genome Wide ◽  
A Genome

scholarly journals EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1510
Author(s):  
Mathis Hildonen ◽  
Amanda M. Levy ◽  
Christine Søholm Hansen ◽  
Jonas Bybjerg-Grauholm ◽  
Axel Skytthe ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Neuropsychiatric Disorders ◽  
Monozygotic Twin ◽  
Mtor Pathway ◽  
Spectrum Disorder ◽  
Genetic Components ◽  
Genome Wide ◽  
Chronic Tic Disorder ◽  
Mtor Signalling

Tic spectrum disorder (TSD) is an umbrella term which includes Gilles de la Tourette syndrome (GTS) and chronic tic disorder (CTD). They are considered highly heritable, yet the genetic components remain largely unknown. In this study we aimed to investigate disease-associated DNA methylation differences to identify genes and pathways which may be implicated in TSD aetiology. For this purpose, we performed an exploratory analysis of the genome-wide DNA methylation patterns in whole blood samples of 16 monozygotic twin pairs, of which eight were discordant and six concordant for TSD, while two pairs were asymptomatic. Although no sites reached genome-wide significance, we identified several sites and regions with a suggestive significance, which were located within or in the vicinity of genes with biological functions associated with neuropsychiatric disorders. The two top genes identified (TSC1 and CRYZ/TYW3) and the enriched pathways and components (phosphoinosides and PTEN pathways, and insulin receptor substrate binding) are related to, or have been associated with, the PI3K/AKT/mTOR pathway. Genes in this pathway have previously been associated with GTS, and mTOR signalling has been implicated in a range of neuropsychiatric disorders. It is thus possible that altered mTOR signalling plays a role in the complex pathogenesis of TSD.

scholarly journals DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins

2015 ◽  
Vol 18 (6) ◽  
pp. 635-646 ◽  
Author(s):  
Pei-Chien Tsai ◽  
Jenny Van Dongen ◽  
Qihua Tan ◽  
Gonneke Willemsen ◽  
Lene Christiansen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Random Effects ◽  
Meta Analysis ◽  
Monozygotic Twins ◽  
Positive Association ◽  
Later Life ◽  
Significant Positive Association ◽  
Association Analyses ◽  
A Genome

Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10−8), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

scholarly journals Epigenetic outlier profiles in depression: A genome-wide DNA methylation analysis of monozygotic twins

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207754 ◽  
Author(s):  
Aldo Córdova-Palomera ◽  
Helena Palma-Gudiel ◽  
Jaume Forés-Martos ◽  
Rafael Tabarés-Seisdedos ◽  
Lourdes Fañanás
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Methylation Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Dna Methylation Analysis

Methylome modifications in monozygotic twins and in depression

2016 ◽  
Vol 33 (S1) ◽  
pp. S30-S30
Author(s):  
L. Fañanás ◽  
A. Córdova-Palomera
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Epidemiological Studies ◽  
P38 Map Kinase ◽  
Biological Processes ◽  
Genome Wide ◽  
Glucocorticoid Signaling ◽  
Analytical Strategies ◽  
Competing Interest

Epigenetics is the study of gene expression changes that are produced by heritable, though potentially reversible, modifications of chromatin structure or DNA methylation. DNA methylation is interesting in epidemiological studies, due to its accessibility and since previous evidence indicates that large inter-individual differences in methylation levels at some loci may correlate with phenotypic plasticity in changing environments.Prior genome-wide methylomic research on depression has suggested that, together with differential DNA methylation changes, affected co-twins of monozygotic twin pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. However, the putative biological roots of this variability remain largely unexplored.This study evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their depressive status. Genome-wide DNA methylation levels were measured in peripheral blood of 34 twins (17 MZ pairs) using Illumina Infinium Human Methylation450 Beadchip. Two analytical strategies were used to identify differentially methylated probes (DMPs) and variably methylated probes (VMPs).The majority of the DMPs were located in genes previously related to neuropsychiatric phenotypes, such as WDR26, a GWAS hit for MDD whose expression levels have been found altered in blood of depressed individuals.VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling.The findings expand on previous research to indicate that both differential and variable methylation may play a role in the etiopathology of depression, and suggest specific genomic loci of potential interest in the epigenetics of depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Equivalent DNA methylation variation between monozygotic co-twins and unrelated individuals reveals universal epigenetic inter-individual dissimilarity

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Benjamin Planterose Jiménez ◽  
Fan Liu ◽  
Amke Caliebe ◽  
Diego Montiel González ◽  
Jordana T. Bell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Measurement Error ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Equivalence Testing ◽  
Sequencing Data ◽  
Stochastic Variation ◽  
Developing Neurons ◽  
Methylation Variation

Abstract Background Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now. Results We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue. Conclusions We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.

scholarly journals Epigenetic Variation in Monozygotic Twins: A Genome-Wide Analysis of DNA Methylation in Buccal Cells

Genes ◽  
2014 ◽  
Vol 5 (2) ◽  
pp. 347-365 ◽  
Author(s):  
Jenny van Dongen ◽  
Erik Ehli ◽  
Roderick Slieker ◽  
Meike Bartels ◽  
Zachary Weber ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Epigenetic Variation ◽  
Buccal Cells ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide analysis of DNA methylation in hypertension-discordant monozygotic twins

2020 ◽  
Author(s):  
Zhentian Wu ◽  
Wenjing Gao ◽  
Weihua Cao ◽  
Chunxiao Li ◽  
Canqing Yu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
Empirical Bayes ◽  
Vegetable Intake ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Main Function ◽  
Genome Wide ◽  
Replication Group ◽  
Pressure Independent

Abstract Background: DNA methylation has great potential for identifying the aetiology of hypertension. The aim of this study was to explore the correlation between hypertension and DNA methylation using twins discordant for hypertension in China. Methods: In this study, 43 pairs of monozygotic twins discordant for hypertension (age 31.9-72.3 years; 67.4% male) from the Chinese National Twin Registry were recruited. Genome-wide DNA methylation was measured using the Illumina Human methylation EPIC Beadchip in whole-blood-derived DNA. Standardized questionnaires were used to collect twin data on the following variables: age, gender, socioeconomic level, lifestyle factors (including smoking, alcohol drinking, vegetable intake, and physical activity). Blood pressure, height, weight, and other anthropometric indicators were obtained by physical examination. Empirical Bayes paired moderated t-test was utilized to compare the methylation data within twin pairs. Results: Four suspected significant methylation sites, cg00950476, cg08041400, cg26733338, and cg08580087 were identified. All of these four sites locate on known loci, which were LINC01252, BDP1, SYT1, and ODZ4, respectively. The main function includes transcriptional regulation, learning and cognitive, neurodevelopment. The significant sites were further replicated among two different replication population, the first replication population contained 38 hypertension concordant monozygotic twin pairs and 38 non-hypertension concordant monozygotic twin pairs matched in age, sex, region, and birth order, and the second replication group included 21 MZ twin pairs discordant for hypertension . None of them, however, were significant. The methylation variation in the above sites may influence blood pressure, independent of genetic and early-life environmental factors. Conclusions: This study found four suspected methylation sites correlated with hypertension. However, all four sites failed the replication analysis. More hypertension-discordant monozygotic twin pairs are needed to replicate these findings in the future to explore the stability of the results.

scholarly journals Increased DNA methylation variability in rheumatoid arthritis discordant monozygotic twins

2018 ◽  
Author(s):  
Amy P. Webster ◽  
Darren Plant ◽  
Simone Ecker ◽  
Flore Zufferey ◽  
Jordana T. Bell ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Association Studies ◽  
Monozygotic Twins ◽  
Autoimmune Disorder ◽  
Monozygotic Twin ◽  
Autoimmune Disorders ◽  
Healthy Population ◽  
Genome Wide ◽  
Discordant Twins

ABSTRACTBackgroundRheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease discordant monozygotic twin pairs.MethodsGenome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between RA and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.ResultsWe have identified a differentially variable DNA methylation signature, that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.ConclusionsThrough genome-wide analysis of DNA methylation in disease discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.

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