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Epigenome wide association

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https://www.readbyqxmd.com/read/28931564/towards-precision-medicine-for-hypertension-a-review-of-genomic-epigenomic-and-microbiomic-effects-on-blood-pressure-in-experimental-rat-models-and-humans
#1
REVIEW
Sandosh Padmanabhan, Bina Joe
Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28928387/bi-directional-effects-of-vitamin-b12-and-methotrexate-on-daphnia-magna-fitness-and-genomic-methylation
#2
Fitore Kusari, Alan M O'Doherty, Nikolas J Hodges, Marcin W Wojewodzic
Here we interrogated, using three separate but complementary experimental approaches, the impact of vitamin B12 availability and methotrexate exposure on Daphnia magna, which we hypothesised should have an opposite effect on One carbon metabolism (OCM). OCM is a vital biological process supporting a variety of physiological processes, including DNA methylation. Contrary to mammalian models, this process remains largely unexplored in invertebrates. The purpose of this study was to elucidate the impact of OCM short-term alteration on the fitness and epigenome of the keystone species, Daphnia...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927277/benchmark-dose-modeling-estimates-of-the-concentrations-of-inorganic-arsenic-that-induce-changes-to-the-neonatal-transcriptome-proteome-and-epigenome-in-a-pregnancy-cohort
#3
Julia Rager, Scott S Auerbach, Grace A Chappell, Elizabeth Martin, Chad Thompson, Rebecca C Fry
Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling...
September 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#4
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28918100/transcriptomic-and-epigenomic-biomarkers-of-antidepressant-response
#5
REVIEW
Raoul Belzeaux, Rixing Lin, Chelsey Ju, Marc-Aurele Chay, Laura M Fiori, Pierre-Eric Lutz, Gustavo Turecki
BACKGROUND: Antidepressant treatment is associated with a high rate of poor response, and thus, biomarker development is warranted. METHODS: We aimed to synthesize studies investigating gene expression, small RNAs, and epigenomic biomarkers of antidepressant response. We conducted a narrative review of the literature. RESULTS: Firstly, we detailed the challenges involved, in terms of biological tissues, relevant study time frames, and mandatory statistical tools...
September 8, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28915241/the-relative-contribution-of-dna-methylation-and-genetic-variants-on-protein-biomarkers-for-human-diseases
#6
Muhammad Ahsan, Weronica E Ek, Mathias Rask-Andersen, Torgny Karlsson, Allan Lind-Thomsen, Stefan Enroth, Ulf Gyllensten, Åsa Johansson
Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs...
September 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28905855/new-insights-into-the-epigenetics-of-inflammatory-rheumatic-diseases
#7
REVIEW
Esteban Ballestar, Tianlu Li
Over the past decade, awareness of the importance of epigenetic alterations in the pathogenesis of rheumatic diseases has grown in parallel with a general recognition of the fundamental role of epigenetics in the regulation of gene expression. Large-scale efforts to generate genome-wide maps of epigenetic modifications in different cell types, as well as in physiological and pathological contexts, illustrate the increasing recognition of the relevance of epigenetics. To date, although several reports have demonstrated the occurrence of epigenetic alterations in a wide range of inflammatory rheumatic conditions, epigenomic information is rarely used in a clinical setting...
September 14, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#8
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28899353/tissue-specific-dna-methylation-is-conserved-across-human-mouse-and-rat-and-driven-by-primary-sequence-conservation
#9
Jia Zhou, Renee L Sears, Xiaoyun Xing, Bo Zhang, Daofeng Li, Nicole B Rockweiler, Hyo Sik Jang, Mayank N K Choudhary, Hyung Joo Lee, Rebecca F Lowdon, Jason Arand, Brianne Tabers, C Charles Gu, Theodore J Cicero, Ting Wang
BACKGROUND: Uncovering mechanisms of epigenome evolution is an essential step towards understanding the evolution of different cellular phenotypes. While studies have confirmed DNA methylation as a conserved epigenetic mechanism in mammalian development, little is known about the conservation of tissue-specific genome-wide DNA methylation patterns. RESULTS: Using a comparative epigenomics approach, we identified and compared the tissue-specific DNA methylation patterns of rat against those of mouse and human across three shared tissue types...
September 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28883893/the-association-between-alu-hypomethylation-and-severity-of-type-2-diabetes-mellitus
#10
Jirapan Thongsroy, Maturada Patchsung, Apiwat Mutirangura
BACKGROUND: Cellular senescence due to genomic instability is believed to be one of the mechanisms causing health problems in diabetes mellitus (DM). Low methylation levels of Alu elements or Alu hypomethylation, an epigenomic event causing genomic instability, were commonly found in aging people and patients with aging phenotypes, such as osteoporosis. RESULTS: We investigate Alu methylation levels of white blood cells of type 2 DM, pre-DM, and control. The DM group possess the lowest Alu methylation (P < 0...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28881982/association-testing-of-bisulfite-sequencing-methylation-data-via-a-laplace-approximation
#11
Omer Weissbrod, Elior Rahmani, Regev Schweiger, Saharon Rosset, Eran Halperin
Motivation: Epigenome-wide association studies can provide novel insights into the regulation of genes involved in traits and diseases. The rapid emergence of bisulfite-sequencing technologies enables performing such genome-wide studies at the resolution of single nucleotides. However, analysis of data produced by bisulfite-sequencing poses statistical challenges owing to low and uneven sequencing depth, as well as the presence of confounding factors. The recently introduced Mixed model Association for Count data via data AUgmentation (MACAU) can address these challenges via a generalized linear mixed model when confounding can be encoded via a single variance component...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28879854/treating-genetic-disorders-using-state-of-the-art-technology
#12
Muhammad Jamal, Arif Ullah, Muhammad Ahsan, Rohit Tyagi, Zeshan Habib, Faheem Ahmad Khan, Khaista Rehman
CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated Protein 9), basically a bacterial immune system is now widely applicable to engineer genomes of a number of cells and organisms because of its simplicity and robustness. In research avenue the system has been optimized to regulate gene expression, modify epigenome and edit target locus. These applications make CRISPR/Cas9, a technology of choice to edit disease causing mutations as well as the epigenome more efficiently than ever before...
September 7, 2017: Current Issues in Molecular Biology
https://www.readbyqxmd.com/read/28869584/an-xqtl-map-integrates-the-genetic-architecture-of-the-human-brain-s-transcriptome-and-epigenome
#13
Bernard Ng, Charles C White, Hans-Ulrich Klein, Solveig K Sieberts, Cristin McCabe, Ellis Patrick, Jishu Xu, Lei Yu, Chris Gaiteri, David A Bennett, Sara Mostafavi, Philip L De Jager
We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28867284/crp-polymorphisms-and-dna-methylation-of-the-aim2-gene-influence-associations-between-trauma-exposure-ptsd-and-c-reactive-protein
#14
M W Miller, H Maniates, E J Wolf, M W Logue, S A Schichman, A Stone, W Milberg, R McGlinchey
BACKGROUND: Recent studies have implicated inflammatory processes in the pathophysiology of posttraumatic stress disorder (PTSD). C-reactive protein (CRP) is a widely-used measure of peripheral inflammation, but little is known about the genetic and epigenetic factors that influence blood levels of C-reactive protein (CRP) in individuals with PTSD. METHODS: Participants were 286 U.S. military veterans of post-9/11 conflicts (57% with current PTSD). Analyses focused on single nucleotide polymorphisms (SNPs) in the CRP gene and DNA methylation at cg10636246 in AIM2-a locus recently linked to CRP levels through results from a large-scale epigenome-wide association study...
August 31, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28858830/exposure-to-low-levels-of-lead-in-utero-and-umbilical-cord-blood-dna-methylation-in-project-viva-an-epigenome-wide-association-study
#15
Shaowei Wu, Marie-France Hivert, Andres Cardenas, Jia Zhong, Sheryl L Rifas-Shiman, Golareh Agha, Elena Colicino, Allan C Just, Chitra Amarasiriwardena, Xihong Lin, Augusto A Litonjua, Dawn L DeMeo, Matthew W Gillman, Robert O Wright, Emily Oken, Andrea A Baccarelli
BACKGROUND: Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. OBJECTIVES: We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U...
August 25, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28854564/epigenome-wide-analysis-of-dna-methylation-in-lung-tissue-shows-concordance-with-blood-studies-and-identifies-tobacco-smoke-inducible-enhancers
#16
Theresa Ryan Stueve, Wen-Qing Li, Jianxin Shi, Crystal N Marconett, Tongwu Zhang, Chenchen Yang, Daniel Mullen, Chunli Yan, William Wheeler, Xing Hua, Beiyun Zhou, Zea Borok, Neil E Caporaso, Angela C Pesatori, Jubao Duan, Ite A Laird-Offringa, Maria Teresa Landi
Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas...
August 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28843141/dna-methylation-and-exposure-to-ambient-air-pollution-in-two-prospective-cohorts
#17
Michelle Plusquin, Florence Guida, Silvia Polidoro, Roel Vermeulen, Ole Raaschou-Nielsen, Gianluca Campanella, Gerard Hoek, Soterios A Kyrtopoulos, Panagiotis Georgiadis, Alessio Naccarati, Carlotta Sacerdote, Vittorio Krogh, H Bas Bueno-de-Mesquita, W M Monique Verschuren, Sergi Sayols-Baixeras, Tommaso Panni, Annette Peters, Dennie G A J Hebels, Jos Kleinjans, Paolo Vineis, Marc Chadeau-Hyam
Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes...
August 23, 2017: Environment International
https://www.readbyqxmd.com/read/28838933/epigenome-wide-association-study-identifies-cardiac-gene-patterning-and-a-novel-class-of-biomarkers-for-heart-failure
#18
Benjamin Meder, Jan Haas, Farbod Sedaghat-Hamedani, Elham Kayvanpour, Karen Frese, Alan Lai, Rouven Nietsch, Christina Scheiner, Stefan Mester, Diana Martins Bordalo, Ali Amr, Carsten Dietrich, Dietmar Pils, Dominik Siede, Hauke Hund, Andrea S Bauer, Daniel B Holzer, Arjang Ruhparwar, Matthias Mueller-Hennessen, Dieter Weichenhan, Christoph Plass, Tanja M Weis, Johannes Backs, Maximilian L Wuerstle, Andreas Keller, Hugo A Katus, Andreas E Posch
Background -Biochemical DNA modification resembles a crucial regulatory layer between genetic information, environmental factors and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with Dilated Cardiomyopathy (DCM) and controls. Methods -Infinium HumanMethylation450 was used for high-density epigenome-wide mapping of DNA methylation in left ventricular biopsies and whole peripheral blood of living probands...
August 24, 2017: Circulation
https://www.readbyqxmd.com/read/28835163/an-epigenome-wide-association-study-of-inflammatory-response-to-fenofibrate-in-the-genetics-of-lipid-lowering-drugs-and-diet-network
#19
Nabiha Yusuf, Bertha Hidalgo, Marguerite R Irvin, Jin Sha, Degui Zhi, Hemant K Tiwari, Devin Absher, Donna K Arnett, Stella W Aslibekyan
AIM: Fenofibrate, a PPAR-α inhibitor used for treating dyslipidemia, has well-documented anti-inflammatory effects that vary between individuals. While DNA sequence variation explains some of the observed variability in response, epigenetic patterns present another promising avenue of inquiry due to the biological links between the PPAR-α pathway, homocysteine and S-adenosylmethionine - a source of methyl groups for the DNA methylation reaction. HYPOTHESIS: DNA methylation variation at baseline is associated with the inflammatory response to a short-term fenofibrate treatment...
September 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28831143/genome-wide-comparative-analysis-of-h3k4me3-profiles-between-diploid-and-allotetraploid-cotton-to-refine-genome-annotation
#20
Qi You, Xin Yi, Kang Zhang, Chunchao Wang, Xuelian Ma, Xueyan Zhang, Wenying Xu, Fuguang Li, Zhen Su
Polyploidy is a common evolutionary occurrence in plants. Recently, published genomes of allotetraploid G. hirsutum and its donors G. arboreum and G. raimondii make cotton an accessible polyploid model. This study used chromatin immunoprecipitation with high-throughput sequencing (ChIP-Seq) to investigate the genome-wide distribution of H3K4me3 in G. arboreum and G. hirsutum, and explore the conservation and variation of genome structures between diploid and allotetraploid cotton. Our results showed that H3K4me3 modifications were associated with active transcription in both cottons...
August 22, 2017: Scientific Reports
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