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Epigenome wide association

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https://www.readbyqxmd.com/read/28535307/intergenerational-impact-of-paternal-lifetime-exposures-to-both-folic-acid-deficiency-and-supplementation-on-reproductive-outcomes-and-imprinted-gene-methylation
#1
Lundi Ly, Donovan Chan, Mahmoud Aarabi, Mylène Landry, Nathalie A Behan, Amanda J MacFarlane, Jacquetta Trasler
STUDY QUESTION: Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? SUMMARY ANSWER: Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation...
May 23, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28535255/tea-and-coffee-consumption-in-relation-to-dna-methylation-in-four-european-cohorts
#2
Weronica E Ek, Elmar W Tobi, Muhammad Ahsan, Erik Lampa, Erica Ponzi, Soterios A Kyrtopoulos, Panagiotis Georgiadis, L H Lumey, Bastiaan T Heijmans, Maria Botsivali, Ingvar A Bergdahl, Torgny Karlsson, Mathias Rask-Andersen, Domenico Palli, Erik Ingelsson, Åsa K Hedman, Lena M Nilsson, Paolo Vineis, Lars Lind, James M Flanagan, Åsa Johansson
Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096)...
May 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28528960/prenatal-stress-and-epigenetics
#3
REVIEW
L Cao-Lei, S R De Rooij, S King, S G Matthews, G A S Metz, T J Roseboom, M Szyf
In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations and which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations...
May 18, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#4
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28523553/dna-modifications-and-alzheimer-s-disease
#5
Rebecca G Smith, Katie Lunnon
Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide. While a number of studies have focused on identifying genetic variants that contribute to the development and progression of late-onset AD, the majority of these only have a relatively small effect size. There are also a number of other risk factors, for example, age, gender, and other comorbidities; however, how these influence disease risk is not known. Therefore, in recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523545/anxiety-and-epigenetics
#6
Andrew A Bartlett, Rumani Singh, Richard G Hunter
Anxiety disorders are highly prevalent psychiatric disorders often comorbid with depression and substance abuse. Twin studies have shown that anxiety disorders are moderately heritable. Yet, genome-wide association studies (GWASs) have failed to identify gene(s) significantly associated with diagnosis suggesting a strong role for environmental factors and the epigenome. A number of anxiety disorder subtypes are considered "stress related." A large focus of research has been on the epigenetic and anxiety-like behavioral consequences of stress...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522454/multiomic-disease-signatures-converge-to-cytotoxic-cd8-t-cells-in-primary-sj%C3%A3-gren-s-syndrome
#7
Shinya Tasaki, Katsuya Suzuki, Ayumi Nishikawa, Yoshiaki Kassai, Maiko Takiguchi, Rina Kurisu, Yuumi Okuzono, Takahiro Miyazaki, Masaru Takeshita, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Kazuhiro Ikeura, Kazuyuki Tsunoda, Rimpei Morita, Akihiko Yoshimura, Hiroyoshi Toyoshiba, Tsutomu Takeuchi
OBJECTIVES: Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology. METHODS: We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. RESULTS: Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins...
May 18, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28517979/cell-type-deconvolution-in-epigenome-wide-association-studies-a-review-and-recommendations
#8
Andrew E Teschendorff, Shijie C Zheng
A major challenge faced by epigenome-wide association studies (EWAS) is cell-type heterogeneity. As many EWAS have already demonstrated, adjusting for changes in cell-type composition can be critical when analyzing and interpreting findings from such studies. Because of their importance, a great number of different statistical algorithms, which adjust for cell-type composition, have been proposed. Some of the methods are 'reference based' in that they require a priori defined reference DNA methylation profiles of cell types that are present in the tissue of interest, while other algorithms are 'reference free...
May 2017: Epigenomics
https://www.readbyqxmd.com/read/28515798/epigenome-wide-association-of-myocardial-infarction-with-dna-methylation-sites-at-loci-related-to-cardiovascular-disease
#9
Masahiro Nakatochi, Sahoko Ichihara, Ken Yamamoto, Keiko Naruse, Shigeki Yokota, Hiroyuki Asano, Tatsuaki Matsubara, Mitsuhiro Yokota
BACKGROUND: Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial infarction (MI), we performed an epigenome-wide association study for this condition in elderly Japanese subjects. A total of 192 case subjects with MI and 192 control subjects were recruited from hospital attendees and the general population, respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from whole blood were obtained by analysis with an Infinium HumanMethylation450 BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28514750/epigenome-wide-association-study-in-hepatocellular-carcinoma-identification-of-stochastic-epigenetic-mutations-through-an-innovative-statistical-approach
#10
REVIEW
Davide Gentilini, Stefania Scala, Germano Gaudenzi, Paolo Garagnani, Miriam Capri, Matteo Cescon, Gian Luca Grazi, Maria Giulia Bacalini, Serena Pisoni, Alessandra Dicitore, Luisa Circelli, Sara Santagata, Francesco Izzo, Anna Maria Di Blasio, Luca Persani, Claudio Franceschi, Giovanni Vitale
Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512992/association-of-cd8-t-cells-with-bone-erosion-in-patients-with-rheumatoid-arthritis
#11
Young Bin Joo, Youngho Park, Kwangwoo Kim, So-Young Bang, Sang-Cheol Bae, Hye-Soon Lee
AIM: Bone erosion is a major problem worsening quality of rheumatoid arthritis (RA) patients' lives. However, causal factors responsible for bone erosion in RA have remained unclear. We aimed to examine genetic variants conferring bone erosion in RA using a Korean genome-wide association study (GWAS) and to search for possible biological mechanisms underlying the development of bone erosion. METHOD: We obtained genome-wide single nucleotide polymorphism (SNP) data for 711 Korean RA patients using Illumina HapMap 550v3/660W arrays...
May 16, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28509669/genetic-advances-in-systemic-lupus-erythematosus-an-update
#12
Lingyan Chen, David L Morris, Timothy J Vyse
PURPOSE OF REVIEW: More than 80 susceptibility loci are now reported to show robust genetic association with systemic lupus erythematosus (SLE). The differential functional effects of the risk alleles for the majority of these loci remain to be defined. Here, we review current SLE association findings and the recent progress in the annotation of noncoding regions of the human genome as well as the new technologies and statistical methods that can be applied to further the understanding of SLE genetics...
May 15, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28500050/a-systemic-analysis-of-transcriptomic-and-epigenomic-data-to-reveal-regulation-patterns-for-complex-disease
#13
Chao Xu, Ji-Gang Zhang, Dongdong Lin, Lan Zhang, Hui Shen, Hong-Wen Deng
Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi-)genomic factors from diverse omics data; and (iii) Until present, the combination of >2 omics datasets has been poorly explored...
May 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28499412/genome-wide-dna-methylation-analysis-reveals-hypomethylation-in-the-low-cpg-promoter-regions-in-lymphoblastoid-cell-lines
#14
Itsuki Taniguchi, Chihiro Iwaya, Keizo Ohnaka, Hiroki Shibata, Ken Yamamoto
BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases...
May 12, 2017: Human Genomics
https://www.readbyqxmd.com/read/28476633/dna-methylation-in-lung-tissues-of-mouse-offspring-exposed-in-utero-to-polycyclic-aromatic-hydrocarbons
#15
Trevor J Fish, Abby D Benninghoff
Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and are suspected lung carcinogens in humans. Moreover, evidence from cell-based studies points to PAHs as modulators of the epigenome. The objective of this work was to assess patterns of genome-wide DNA methylation in lung tissues of adult offspring initiated in utero with the transplacental PAH carcinogens dibenzo [def,p]chrysene (DBC) or benzo [a]pyrene (BaP). Genome-wide methylation patterns for normal (not exposed), normal adjacent and lung tumor tissues obtained from adult offspring were determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen mouse DNA methylation CpG island array...
May 2, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28475762/epigenome-wide-association-study-of-rheumatoid-arthritis-identifies-differentially-methylated-loci-in-b-cells
#16
Antonio Julià, Devin Absher, María López-Lasanta, Nuria Palau, Andrea Pluma, Lindsay Waite Jones, John R Glossop, William E Farrell, Richard M Myers, Sara Marsal
Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like Rheumatoid Arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells...
May 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28470095/impact-of-confounding-by-leukocyte-composition-on-associations-of-leukocyte-dna-methylation-with-common-risk-factors
#17
Jonathan Alexander Heiss, Hermann Brenner
AIM: One concern in epigenome-wide studies investigating leukocyte DNA methylation is that observed associations may at least partly reflect differences in leukocyte composition (LC) rather than changes in methylation. We estimated the magnitude of confounding by LC for common risk factors and diseases. MATERIALS & METHODS: Variation of LC according to sex, race, age, smoking, alcohol consumption, BMI, cardiovascular fitness, hypertension, coronary heart disease and diabetes was analyzed using blood differentials from 4117 participants of NHANES...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28463415/using-chromatin-immunoprecipitation-in-toxicology-a-step-by-step-guide-to-increasing-efficiency-reducing-variability-and-expanding-applications
#18
Shaun D McCullough, Doan M On, Emma C Bowers
Histone modifications work in concert with DNA methylation to regulate cellular structure, function, and response to environmental stimuli. More than 130 unique histone modifications have been described to date, and chromatin immunoprecipitation (ChIP) allows for the exploration of their associations with the regulatory regions of target genes and other DNA/chromatin-associated proteins across the genome. Many variations of ChIP have been developed in the 30 years since its earliest version came into use, which makes it challenging for users to integrate the procedure into their research programs...
May 2, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28460026/epigenomic-and-transcriptomic-approaches-in-the-post-genomic-era-path-to-novel-targets-for-diagnosis-and-therapy-of-the-ischaemic-heart-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#19
Cinzia Perrino, Albert-Laszló Barabási, Gianluigi Condorelli, Sean Michael Davidson, Leon De Windt, Stefanie Dimmeler, Felix Benedikt Engel, Derek John Hausenloy, Joseph Addison Hill, Linda Wilhelmina Van Laake, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Manuel Mayr, Fabrice Prunier, Joost Petrus Geradus Sluijter, Rainer Schulz, Thomas Thum, Kirsti Ytrehus, Péter Ferdinandy
Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets...
June 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28459462/genome-wide-dna-methylation-profiling-reveals-cancer-associated-changes-within-early-colonic-neoplasia
#20
M P Hanley, M A Hahn, A X Li, X Wu, J Lin, J Wang, A H Choi, Z Ouyang, Y Fong, G P Pfeifer, T J Devers, D W Rosenberg
Colorectal cancer (CRC) is characterized by genome-wide alterations to DNA methylation that influence gene expression and genomic stability. Less is known about the extent to which methylation is disrupted in the earliest stages of CRC development. In this study, we have combined laser-capture microdissection with reduced representation bisulfite sequencing to identify cancer-associated DNA methylation changes in human aberrant crypt foci (ACF), the earliest putative precursor to CRC. Using this approach, methylation profiles have been generated for 10 KRAS-mutant ACF and 10 CRCs harboring a KRAS mutation, as well as matched samples of normal mucosa...
May 1, 2017: Oncogene
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