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Epigenome wide association

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https://www.readbyqxmd.com/read/28637314/dna-methylation-signatures-and-coagulation-factors-in-the-peripheral-blood-leucocytes-of-epithelial-ovarian-cancer
#1
Lian Li, Hong Zheng, Yubei Huang, Caiyun Huang, Shuang Zhang, Jing Tian, Pei Li, Anil K Sood, Wei Zhang, Kexin Chen
Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, RNA, proteins, and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485,000 CpG sites in peripheral blood in 24 epithelial ovarian cancer cases and 24 age-matched healthy controls...
June 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28637190/evolution-of-the-sperm-methylome-of-primates-is-associated-with-retrotransposon-insertions-and-genome-instability
#2
Kei Fukuda, Yukihiro Inoguchi, Kenji Ichiyanagi, Tomoko Ichiyanagi, Yasuhiro Go, Masashi Nagano, Yojiro Yanagawa, Noboru Takaesu, Yasuyuki Ohkawa, Hiroo Imai, Hiroyuki Sasaki
Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpanzees, which have a 1.2% DNA sequence divergence, of sperm, the frontal cortices, B cells, and neutrophils. We revealed that species-specific differentially methylated regions (S-DMRs), ranging from several hundred bp to several kb, were frequently associated with sequence changes in transcription factor binding sites and insertions of Alu and SVA retrotransposons...
June 20, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28629478/genetic-epigenetic-interactions-in-cis-a-major-focus-in-the-post-gwas-era
#3
REVIEW
Catherine Do, Alyssa Shearer, Masako Suzuki, Mary Beth Terry, Joel Gelernter, John M Greally, Benjamin Tycko
Studies on genetic-epigenetic interactions, including the mapping of methylation quantitative trait loci (mQTLs) and haplotype-dependent allele-specific DNA methylation (hap-ASM), have become a major focus in the post-genome-wide-association-study (GWAS) era. Such maps can nominate regulatory sequence variants that underlie GWAS signals for common diseases, ranging from neuropsychiatric disorders to cancers. Conversely, mQTLs need to be filtered out when searching for non-genetic effects in epigenome-wide association studies (EWAS)...
June 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28624579/epigenome-wide-association-study-identifies-methylation-sites-associated-with-liver-enzymes-and-hepatic-steatosis
#4
Jana Nano, Mohsen Ghanbari, Wenshi Wang, Paul S de Vries, Klodian Dhana, Taulant Muka, André G Uitterlinden, Joyce B J van Meurs, Albert Hofman, Oscar H Franco, Qiuwei Pan, Sarwa Darwish Murad, Abbas Dehghan
BACKGROUND & AIMS: Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. METHODS: We conducted an epigenome-wide association study in whole blood for liver enzymes levels including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28621160/epigenome-wide-association-study-of-chronic-obstructive-pulmonary-disease-and-lung-function-in-koreans
#5
Mi Kyeong Lee, Yoonki Hong, Sun-Young Kim, Woo Jin Kim, Stephanie J London
AIM: To identify differentially methylated probes (DMPs) and regions (DMRs) in relation to chronic obstructive pulmonary disease (COPD) and lung function traits. METHODS: We performed an epigenome-wide association study of COPD and spirometric parameters, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC, in blood DNA using the Infinium HumanMethylation450 (n = 100, a Korean COPD cohort). RESULTS: We found one significant DMP (cg03559389, DIP2C) and 104 significant DMRs after multiple-testing correction...
June 16, 2017: Epigenomics
https://www.readbyqxmd.com/read/28611825/epigenetic-combinatorial-patterns-predict-disease-variants
#6
Yu Zhang
Most genetic variants identified in genome-wide association studies are noncoding and are likely tagging nearby causal variants. It is a challenging task to pinpoint the precise locations of disease-causal variants and understand their functions in disease. A promising approach to improve fine mapping is to integrate the functional data currently available on hundreds of human tissues and cell types. Although there are several methods that use functional data to prioritize disease variants, they mainly use linear models, or equivalent naive likelihood-based models for prediction...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28604729/dnmt-and-hdac-inhibitors-induce-cryptic-transcription-start-sites-encoded-in-long-terminal-repeats
#7
David Brocks, Christopher R Schmidt, Michael Daskalakis, Hyo Sik Jang, Nakul M Shah, Daofeng Li, Jing Li, Bo Zhang, Yiran Hou, Sara Laudato, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Md Saiful Islam, Anders M Lindroth, Simon Haas, Marieke Essers, Charles D Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Jan-Philipp Mallm, Karsten Rippe, Rainer Will, Dieter Weichenhan, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions...
June 12, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28603561/distinct-dna-methylation-profiles-in-subtypes-of-orofacial-cleft
#8
Gemma C Sharp, Karen Ho, Amy Davies, Evie Stergiakouli, Kerry Humphries, Wendy McArdle, Jonathan Sandy, George Davey Smith, Sarah J Lewis, Caroline L Relton
BACKGROUND: Epigenetic data could help identify risk factors for orofacial clefts, either by revealing a causal role for epigenetic mechanisms in causing clefts or by capturing information about causal genetic or environmental factors. Given the evidence that different subtypes of orofacial cleft have distinct aetiologies, we explored whether children with different cleft subtypes showed distinct epigenetic profiles. METHODS: In whole-blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28594818/leveraging-functional-annotations-in-genetic-risk-prediction-for-human-complex-diseases
#9
Yiming Hu, Qiongshi Lu, Ryan Powles, Xinwei Yao, Can Yang, Fang Fang, Xinran Xu, Hongyu Zhao
Genetic risk prediction is an important goal in human genetics research and precision medicine. Accurate prediction models will have great impacts on both disease prevention and early treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome wide association studies (GWAS), genetic risk prediction accuracy remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes in the presence of linkage disequilibrium...
June 8, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28587674/navise-superenhancer-navigator-integrating-epigenomics-signal-algebra
#10
Alex M Ascensión, Mikel Arrospide-Elgarresta, Ander Izeta, Marcos J Araúzo-Bravo
BACKGROUND: Superenhancers are crucial structural genomic elements determining cell fate, and they are also involved in the determination of several diseases, such as cancer or neurodegeneration. Although there are pipelines which use independent pieces of software to predict the presence of superenhancers from genome-wide chromatin marks or DNA-interaction protein binding sites, there is not yet an integrated software tool that processes automatically algebra combinations of raw data sequencing into a comprehensive final annotated report of predicted superenhancers...
June 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28581336/challenges-and-progress-in-interpretation-of-non-coding-genetic-variants-associated-with-human-disease
#11
Yizhou Zhu, Cagdas Tazearslan, Yousin Suh
Genome-wide association studies have shown that the far majority of disease-associated variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes contribute to disease risk. To identify truly causal non-coding variants and their affected target genes remains challenging but is a critical step to translate the genetic associations to molecular mechanisms and ultimately clinical applications. Here we review genomic/epigenomic resources and in silico tools that can be used to identify causal non-coding variants and experimental strategies to validate their functionalities...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28577936/association-between-dna-methylation-and-coronary-heart-disease-or-other-atherosclerotic-events-a-systematic-review
#12
REVIEW
Alba Fernández-Sanlés, Sergi Sayols-Baixeras, Isaac Subirana, Irene R Degano, Roberto Elosua
BACKGROUND AND AIMS: The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits. METHODS: A systematic review was designed. The condition of interest was DNA methylation, and the outcome was CHD or other atherosclerosis-related traits. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS)...
May 18, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28576882/modeling-gene-regulation-from-paired-expression-and-chromatin-accessibility-data
#13
Zhana Duren, Xi Chen, Rui Jiang, Yong Wang, Wing Hung Wong
The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28575352/dna-methylation-signatures-in-cord-blood-of-icsi-children
#14
Nady El Hajj, Larissa Haertle, Marcus Dittrich, Sarah Denk, Harald Lehnen, Thomas Hahn, Martin Schorsch, Thomas Haaf
STUDY QUESTION: Does ICSI induce specific DNA methylation changes in the resulting offspring? SUMMARY ANSWER: Although several thousand analyzed CpG sites (throughout the genome) displayed significant between-group methylation differences, both ICSI and spontaneously conceived children varied within the normal range of methylation variation. WHAT IS KNOWN ALREADY: Children conceived by ART have increased risks for medical problems at birth and to the extent of present knowledge also in later life (i...
May 31, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28572861/genome-wide-dna-methylation-profiling-integrated-with-gene-expression-profiling-identifies-pax9-as-a-novel-prognostic-marker-in-chronic-lymphocytic-leukemia
#15
Lata Rani, Nitin Mathur, Ritu Gupta, Ajay Gogia, Gurvinder Kaur, Jaspreet Kaur Dhanjal, Durai Sundar, Lalit Kumar, Atul Sharma
BACKGROUND: In chronic lymphocytic leukemia (CLL), epigenomic and genomic studies have expanded the existing knowledge about the disease biology and led to the identification of potential biomarkers relevant for implementation of personalized medicine. In this study, an attempt has been made to examine and integrate the global DNA methylation changes with gene expression profile and their impact on clinical outcome in early stage CLL patients. RESULTS: The integration of DNA methylation profile (n = 14) with the gene expression profile (n = 21) revealed 142 genes as hypermethylated-downregulated and; 62 genes as hypomethylated-upregulated in early stage CLL patients compared to CD19+ B-cells from healthy individuals...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28555657/associating-cellular-epigenetic-models-with-human-phenotypes
#16
REVIEW
Tuuli Lappalainen, John M Greally
Epigenetic association studies have been carried out to test the hypothesis that environmental perturbations trigger cellular reprogramming, with downstream effects on cellular function and phenotypes. There have now been numerous studies of the potential molecular mediators of epigenetic changes by epigenome-wide association studies (EWAS). However, a challenge for the field is the interpretation of the results obtained. We describe a second-generation EWAS approach, which focuses on the possible cellular models of epigenetic perturbations, studied by rigorous analysis and interpretation of genomic data...
July 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28549425/fast-and-robust-adjustment-of-cell-mixtures-in-epigenome-wide-association-studies-with-smartsva
#17
Jun Chen, Ehsan Behnam, Jinyan Huang, Miriam F Moffatt, Daniel J Schaid, Liming Liang, Xihong Lin
BACKGROUND: One problem that plagues epigenome-wide association studies is the potential confounding due to cell mixtures when purified target cells are not available. Reference-free adjustment of cell mixtures has become increasingly popular due to its flexibility and simplicity. However, existing methods are still not optimal: increased false positive rates and reduced statistical power have been observed in many scenarios. METHODS: We develop SmartSVA, an optimized surrogate variable analysis (SVA) method, for fast and robust reference-free adjustment of cell mixtures...
May 26, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28543738/crispr-editing-in-biological-and-biomedical-investigation
#18
Xing-Da Ju, Jing Xu, Zhong Sheng Sun
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR--associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28540928/anxiety-associated-increased-cpg-methylation-in-the-promoter-of-asb1-a-translational-approach-evidenced-by-epidemiological-and-clinical-studies-and-a-murine-model
#19
Rebecca T Emeny, Jens Baumert, Anthony S Zannas, Sonja Kunze, Simone Wahl, Stella Iurato, Janine Arloth, Angelika Erhardt, Georgia Balsevich, Mathias V Schmidt, Peter Weber, Anja Kretschmer, Liliane Pfeiffer, Johannes Kruse, Konstantin Strauch, Michael Roden, Christian Herder, Wolfgang Koenig, Christian Gieger, Melanie Waldenberger, Annette Peters, Elisabeth B Binder, Karl-Heinz Ladwig
Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450 K BeadChip) and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation...
May 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#20
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
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