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Epigenome wide association

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https://www.readbyqxmd.com/read/27909437/differentially-methylated-dna-regions-in-monozygotic-twin-pairs-discordant-for-rheumatoid-arthritis-an-epigenome-wide-study
#1
Anders J Svendsen, Kristina Gervin, Robert Lyle, Lene Christiansen, Kirsten Kyvik, Peter Junker, Christian Nielsen, Gunnar Houen, Qihua Tan
OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27906046/chromatin-landscapes-and-genetic-risk-in-systemic-lupus
#2
Joyce S Hui-Yuen, Lisha Zhu, Lai Ping Wong, Kaiyu Jiang, Yanmin Chen, Tao Liu, James N Jarvis
BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27898055/increased-dna-methylation-variability-in-type-1-diabetes-across-three-immune-effector-cell-types
#3
Dirk S Paul, Andrew E Teschendorff, Mary A N Dang, Robert Lowe, Mohammed I Hawa, Simone Ecker, Huriya Beyan, Stephanie Cunningham, Alexandra R Fouts, Anita Ramelius, Frances Burden, Samantha Farrow, Sophia Rowlston, Karola Rehnstrom, Mattia Frontini, Kate Downes, Stephan Busche, Warren A Cheung, Bing Ge, Marie-Michelle Simon, David Bujold, Tony Kwan, Guillaume Bourque, Avik Datta, Ernesto Lowy, Laura Clarke, Paul Flicek, Emanuele Libertini, Simon Heath, Marta Gut, Ivo G Gut, Willem H Ouwehand, Tomi Pastinen, Nicole Soranzo, Sabine E Hofer, Beate Karges, Thomas Meissner, Bernhard O Boehm, Corrado Cilio, Helena Elding Larsson, Åke Lernmark, Andrea K Steck, Vardhman K Rakyan, Stephan Beck, R David Leslie
The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially variable CpG positions (DVPs) in T1D twins when compared with their healthy co-twins and when compared with healthy, unrelated individuals...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27895805/blood-based-dna-methylation-as-biomarker-for-breast-cancer-a-systematic-review
#4
REVIEW
Qiuqiong Tang, Jie Cheng, Xue Cao, Harald Surowy, Barbara Burwinkel
Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27892496/ewas-epigenome-wide-association-studies-software-1-0-identifying-the-association-between-combinations-of-methylation-levels-and-diseases
#5
Jing Xu, Di Liu, Linna Zhao, Ying Li, Zhaoyang Wang, Yang Chen, Changgui Lei, Lin Gao, Fanwu Kong, Lijun Yuan, Yongshuai Jiang
Similar to the SNP (single nucleotide polymorphism) data, there is non-random association of the DNA methylation level (we call it methylation disequilibrium, MD) between neighboring methylation loci. For the case-control study of complex diseases, it is important to identify the association between methylation levels combination types (we call it methylecomtype) and diseases/phenotypes. We extended the classical framework of SNP haplotype-based association study in population genetics to DNA methylation level data, and developed a software EWAS to identify the disease-related methylecomtypes...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891191/birth-weight-for-gestational-age-is-associated-with-dna-methylation-at-birth-and-in-childhood
#6
Golareh Agha, Hanine Hajj, Sheryl L Rifas-Shiman, Allan C Just, Marie-France Hivert, Heather H Burris, Xihong Lin, Augusto A Litonjua, Emily Oken, Dawn L DeMeo, Matthew W Gillman, Andrea A Baccarelli
BACKGROUND: Both higher and lower fetal growth are associated with cardio-metabolic health later in life, suggesting that prenatal developmental programming determines long-term cardiovascular disease risk. Epigenetic mechanisms, which orchestrate fetal growth and development, may offer insight on the early programming of health and disease. We investigated whether birth weight-for-gestational is associated with DNA methylation at birth and mid-childhood, measured via the Infinium 450K array...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27887572/maternal-smoking-impacts-key-biological-pathways-in-newborns-through-epigenetic-modification-in-utero
#7
Daniel M Rotroff, Bonnie R Joubert, Skylar W Marvel, Siri E Håberg, Michael C Wu, Roy M Nilsen, Per M Ueland, Wenche Nystad, Stephanie J London, Alison Motsinger-Reif
BACKGROUND: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine...
November 25, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27886174/5-hydroxymethylcytosine-localizes-to-enhancer-elements-and-is-associated-with-survival-in-glioblastoma-patients
#8
Kevin C Johnson, E Andres Houseman, Jessica E King, Katharine M von Herrmann, Camilo E Fadul, Brock C Christensen
Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27886173/integrative-epigenome-wide-analysis-demonstrates-that-dna-methylation-may-mediate-genetic-risk-in-inflammatory-bowel-disease
#9
N T Ventham, N A Kennedy, A T Adams, R Kalla, S Heath, K R O'Leary, H Drummond, D C Wilson, I G Gut, E R Nimmo, J Satsangi
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27886132/the-future-is-the-past-methylation-qtls-in-schizophrenia
#10
REVIEW
Anke Hoffmann, Michael Ziller, Dietmar Spengler
Genome-wide association studies (GWAS) have remarkably advanced insight into the genetic basis of schizophrenia (SCZ). Still, most of the functional variance in disease risk remains unexplained. Hence, there is a growing need to map genetic variability-to-genes-to-functions for understanding the pathophysiology of SCZ and the development of better treatments. Genetic variation can regulate various cellular functions including DNA methylation, an epigenetic mark with important roles in transcription and the mediation of environmental influences...
November 24, 2016: Genes
https://www.readbyqxmd.com/read/27884066/training-a-model-for-estimating-leukocyte-composition-using-whole-blood-dna-methylation-and-cell-counts-as-reference
#11
Jonathan A Heiss, Lutz P Breitling, Benjamin Lehne, Jaspal S Kooner, John C Chambers, Hermann Brenner
AIM: Whole-blood DNA methylation depends on the underlying leukocyte composition and confounding hereby is a major concern in epigenome-wide association studies. Cell counts are often missing or may not be feasible. Computational approaches estimate leukocyte composition from DNA methylation based on reference datasets of purified leukocytes. We explored the possibility to train such a model on whole-blood DNA methylation and cell counts without the need for purification. MATERIALS & METHODS: Using whole-blood DNA methylation and corresponding five-part cell counts from 2445 participants from the London Life Sciences Prospective Population Study, a model was trained on a subset of 175 subjects and evaluated on the remaining...
November 25, 2016: Epigenomics
https://www.readbyqxmd.com/read/27876072/high-specificity-bioinformatics-framework-for-epigenomic-profiling-of-discordant-twins-reveals-specific-and-shared-markers-for-acpa-and-acpa-positive-rheumatoid-arthritis
#12
David Gomez-Cabrero, Malin Almgren, Louise K Sjöholm, Aase H Hensvold, Mikael V Ringh, Rakel Tryggvadottir, Juha Kere, Annika Scheynius, Nathalie Acevedo, Lovisa Reinius, Margaret A Taub, Carolina Montano, Martin J Aryee, Jason I Feinberg, Andrew P Feinberg, Jesper Tegnér, Lars Klareskog, Anca I Catrina, Tomas J Ekström
BACKGROUND: Twin studies are powerful models to elucidate epigenetic modifications resulting from gene-environment interactions. Yet, commonly a limited number of clinical twin samples are available, leading to an underpowered situation afflicted with false positives and hampered by low sensitivity. We investigated genome-wide DNA methylation data from two small sets of monozygotic twins representing different phases during the progression of rheumatoid arthritis (RA) to find novel genes for further research...
November 22, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27875981/a-statistical-model-for-the-analysis-of-beta-values-in-dna-methylation-studies
#13
Leonie Weinhold, Simone Wahl, Sonali Pechlivanis, Per Hoffmann, Matthias Schmid
BACKGROUND: The analysis of DNA methylation is a key component in the development of personalized treatment approaches. A common way to measure DNA methylation is the calculation of beta values, which are bounded variables of the form M/(M+U) that are generated by Illumina's 450k BeadChip array. The statistical analysis of beta values is considered to be challenging, as traditional methods for the analysis of bounded variables, such as M-value regression and beta regression, are based on regularity assumptions that are often too strong to adequately describe the distribution of beta values...
November 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27867036/dna-methylation-dynamics-of-human-hematopoietic-stem-cell-differentiation
#14
Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A Choudry, Peter Ebert, Johanna Klughammer, Samantha Farrow, Antonella Santoro, Valerio Ciaurro, Anthony Mathur, Rakesh Uppal, Hendrik G Stunnenberg, Willem H Ouwehand, Elisa Laurenti, Thomas Lengauer, Mattia Frontini, Christoph Bock
Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27866770/tetanus-vaccination-is-associated-with-differential-dna-methylation-reduces-the-risk-of-asthma-in-adolescence
#15
Vimala Devi Janjanam, Nandini Mukherjee, Gabrielle A Lockett, Faisal I Rezwan, Ramesh Kurukulaaratchy, Frances Mitchell, Hongmei Zhang, Hasan Arshad, John W Holloway, Wilfried Karmaus
BACKGROUND: Vaccinations have been suggested to be associated with increased risk of allergic diseases. Tetanus vaccination is one of the most frequently administered vaccines as a part of wound management and was also found to be associated with increased serum IgE levels. We hypothesized that the vaccination modifies the risk of allergic diseases through epigenetic changes such as DNA methylation. METHOD: Data on tetanus vaccination between 10 and 18years of age was collected from a birth cohort established on the Isle of Wight UK in 1989...
December 12, 2016: Vaccine
https://www.readbyqxmd.com/read/27863251/genetic-drivers-of-epigenetic-and-transcriptional-variation-in-human-immune-cells
#16
Lu Chen, Bing Ge, Francesco Paolo Casale, Louella Vasquez, Tony Kwan, Diego Garrido-Martín, Stephen Watt, Ying Yan, Kousik Kundu, Simone Ecker, Avik Datta, David Richardson, Frances Burden, Daniel Mead, Alice L Mann, Jose Maria Fernandez, Sophia Rowlston, Steven P Wilder, Samantha Farrow, Xiaojian Shao, John J Lambourne, Adriana Redensek, Cornelis A Albers, Vyacheslav Amstislavskiy, Sofie Ashford, Kim Berentsen, Lorenzo Bomba, Guillaume Bourque, David Bujold, Stephan Busche, Maxime Caron, Shu-Huang Chen, Warren Cheung, Oliver Delaneau, Emmanouil T Dermitzakis, Heather Elding, Irina Colgiu, Frederik O Bagger, Paul Flicek, Ehsan Habibi, Valentina Iotchkova, Eva Janssen-Megens, Bowon Kim, Hans Lehrach, Ernesto Lowy, Amit Mandoli, Filomena Matarese, Matthew T Maurano, John A Morris, Vera Pancaldi, Farzin Pourfarzad, Karola Rehnstrom, Augusto Rendon, Thomas Risch, Nilofar Sharifi, Marie-Michelle Simon, Marc Sultan, Alfonso Valencia, Klaudia Walter, Shuang-Yin Wang, Mattia Frontini, Stylianos E Antonarakis, Laura Clarke, Marie-Laure Yaspo, Stephan Beck, Roderic Guigo, Daniel Rico, Joost H A Martens, Willem H Ouwehand, Taco W Kuijpers, Dirk S Paul, Hendrik G Stunnenberg, Oliver Stegle, Kate Downes, Tomi Pastinen, Nicole Soranzo
Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14(+) monocytes, CD16(+) neutrophils, and naive CD4(+) T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27858497/high-fat-diet-and-exercise-lead-to-a-disrupted-and-pathogenic-dna-methylome-in-mouse-liver
#17
Dan Zhou, Ryan A Hlady, Marissa J Schafer, Thomas A White, Chen Liu, Jeong-Hyeon Choi, Jordan D Miller, Lewis R Roberts, Nathan K LeBrasseur, Keith D Robertson
High-fat diet consumption and sedentary life style elevates risk for obesity, non-alcoholic fatty liver disease, and cancer. Exercise training conveys health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms in many tissues; however, such effects are poorly documented in the liver, a central metabolic organ. To dissect the consequences of diet and exercise on the liver epigenome, we measured DNA methylation, using reduced representation bisulfite sequencing, and transcription, using RNA-seq, in mice maintained on a fast food diet with sedentary lifestyle or exercise, compared to control diet with and without exercise...
November 18, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27852009/treatment-of-cardiovascular-pathology-with-epigenetically-active-agents-focus-on-natural-and-synthetic-inhibitors-of-dna-methylation-and-histone-deacetylation
#18
REVIEW
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Cardiovascular disease (CVD) retains a leadership as a major cause of human death worldwide. Although a substantial progress was attained in the development of cardioprotective and vasculoprotective drugs, a search for new efficient therapeutic strategies and promising targets is under way. Modulation of epigenetic CVD mechanisms through administration epigenetically active agents is one of such new approaches. Epigenetic mechanisms involve heritable changes in gene expression that are not linked to the alteration of DNA sequence...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27851974/eforge-a-tool-for-identifying-cell-type-specific-signal-in-epigenomic-data
#19
Charles E Breeze, Dirk S Paul, Jenny van Dongen, Lee M Butcher, John C Ambrose, James E Barrett, Robert Lowe, Vardhman K Rakyan, Valentina Iotchkova, Mattia Frontini, Kate Downes, Willem H Ouwehand, Jonathan Laperle, Pierre-Étienne Jacques, Guillaume Bourque, Anke K Bergmann, Reiner Siebert, Edo Vellenga, Sadia Saeed, Filomena Matarese, Joost H A Martens, Hendrik G Stunnenberg, Andrew E Teschendorff, Javier Herrero, Ewan Birney, Ian Dunham, Stephan Beck
Epigenome-wide association studies (EWAS) provide an alternative approach for studying human disease through consideration of non-genetic variants such as altered DNA methylation. To advance the complex interpretation of EWAS, we developed eFORGE (http://eforge.cs.ucl.ac.uk/), a new standalone and web-based tool for the analysis and interpretation of EWAS data. eFORGE determines the cell type-specific regulatory component of a set of EWAS-identified differentially methylated positions. This is achieved by detecting enrichment of overlap with DNase I hypersensitive sites across 454 samples (tissues, primary cell types, and cell lines) from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27851968/analysis-of-normal-human-mammary-epigenomes-reveals-cell-specific-active-enhancer-states-and-associated-transcription-factor-networks
#20
Davide Pellacani, Misha Bilenky, Nagarajan Kannan, Alireza Heravi-Moussavi, David J H F Knapp, Sitanshu Gakkhar, Michelle Moksa, Annaick Carles, Richard Moore, Andrew J Mungall, Marco A Marra, Steven J M Jones, Samuel Aparicio, Martin Hirst, Connie J Eaves
The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines...
November 15, 2016: Cell Reports
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