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Epigenome wide association

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https://www.readbyqxmd.com/read/29164275/dna-methylation-markers-associated-with-type-2-diabetes-fasting-glucose-and-hba1c-levels-a-systematic-review-and-replication-in-a-case-control-sample-of-the-lifelines-study
#1
Eliza Walaszczyk, Mirjam Luijten, Annemieke M W Spijkerman, Marc J Bonder, Helen L Lutgers, Harold Snieder, Bruce H R Wolffenbuttel, Jana V van Vliet-Ostaptchouk
AIMS/HYPOTHESIS: Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study. METHODS: We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results...
November 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/29137428/pten-loss-is-associated-with-prostate-cancer-recurrence-and-alterations-in-tumor-dna-methylation-profiles
#2
Milan S Geybels, Min Fang, Jonathan L Wright, Xiaoyu Qu, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Ziding Feng, Elaine A Ostrander, Peter S Nelson, Janet L Stanford
Background: Prostate cancer (PCa) with loss of the tumor suppressor gene PTEN has an unfavorable prognosis. DNA methylation profiles associated with PTEN loss may provide further insights into the mechanisms underlying these more aggressive, clinically relevant tumors. Methods: The cohort included patients with clinically localized PCa. Samples taken from the primary tumor were used to determine PTEN genomic deletions using FISH, and to analyze epigenome-wide DNA methylation profiles...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129922/statistical-and-integrative-system-level-analysis-of-dna-methylation-data
#3
REVIEW
Andrew E Teschendorff, Caroline L Relton
Epigenetics plays a key role in cellular development and function. Alterations to the epigenome are thought to capture and mediate the effects of genetic and environmental risk factors on complex disease. Currently, DNA methylation is the only epigenetic mark that can be measured reliably and genome-wide in large numbers of samples. This Review discusses some of the key statistical challenges and algorithms associated with drawing inferences from DNA methylation data, including cell-type heterogeneity, feature selection, reverse causation and system-level analyses that require integration with other data types such as gene expression, genotype, transcription factor binding and other epigenetic information...
November 13, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29126224/dbtss-dbkero-for-integrated-analysis-of-transcriptional-regulation
#4
Ayako Suzuki, Shin Kawano, Toutai Mitsuyama, Mikita Suyama, Yae Kanai, Katsuhiko Shirahige, Hiroyuki Sasaki, Katsushi Tokunaga, Katsuya Tsuchihara, Sumio Sugano, Kenta Nakai, Yutaka Suzuki
DBTSS (Database of Transcriptional Start Sites)/DBKERO (Database of Kashiwa Encyclopedia for human genome mutations in Regulatory regions and their Omics contexts) is the database originally initiated with the information of transcriptional start sites and their upstream transcriptional regulatory regions. In recent years, we updated the database to assist users to elucidate biological relevance of the human genome variations or somatic mutations in cancers which may affect the transcriptional regulation. In this update, we facilitate interpretations of disease associated genomic variation, using the Japanese population as a model case...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29125844/significant-associations-between-driver-gene-mutations-and-dna-methylation-alterations-across-many-cancer-types
#5
Yun-Ching Chen, Valer Gotea, Gennady Margolin, Laura Elnitski
Recent evidence shows that mutations in several driver genes can cause aberrant methylation patterns, a hallmark of cancer. In light of these findings, we hypothesized that the landscapes of tumor genomes and epigenomes are tightly interconnected. We measured this relationship using principal component analyses and methylation-mutation associations applied at the nucleotide level and with respect to genome-wide trends. We found that a few mutated driver genes were associated with genome-wide patterns of aberrant hypomethylation or CpG island hypermethylation in specific cancer types...
November 10, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29115576/genome-wide-dna-methylome-alterations-in-acute-coronary-syndrome
#6
Dandan Li, Jing Yan, Yunlong Yuan, Cheng Wang, Jia Wu, Qingwen Chen, Jiaxi Song, Junjun Wang
Acute coronary syndrome (ACS) is a common disease with high mortality and morbidity rates. The methylation status of blood DNA may serve as a potential early diagnosis and prevention biomarker for numerous diseases. The present study was designed to explore novel genome-wide aberrant DNA methylation patterns associated with ACS. The Infinium HumanMethylation450 assay was used to examine genome-wide DNA methylation profiles in 3 pairs of ACS and control group samples. Epigenome-wide DNA methylation, genomic distribution, Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29106447/an-evaluation-of-noncoding-genome-annotation-tools-through-enrichment-analysis-of-15-genome-wide-association-studies
#7
Boyang Li, Qiongshi Lu, Hongyu Zhao
Functionally annotating genetic variations is an essential yet challenging topic in human genetics research. As large consortia including ENCODE and Roadmap Epigenomics Project continue to generate high-throughput transcriptomic and epigenomic data, many computational frameworks have been developed to integrate these experimental data to predict functionality of genetic variations in both protein-coding and noncoding regions. Here, we compare a number of recently developed annotation frameworks for noncoding regions through enrichment analysis on genome-wide association studies (GWASs)...
November 2, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29106300/increased-correlation-between-methylation-sites-in-epigenome-wide-replication-studies-impact-on-analysis-and-results
#8
Maja Popovic, Francesca Fasanelli, Valentina Fiano, Annibale Biggeri, Lorenzo Richiardi
AIM: To show that an increased correlation between CpGs after selection through an epigenome-wide association studies (EWAS) might translate into biased replication results. METHODS: Pairwise correlation coefficients between CpGs selected in two published EWAS, the top hits replication, Bonferroni p-values, Benjamini-Hochberg (BH) false discovery rate (FDR) and directional FDR r-values were calculated in the NINFEA cohort data. Exposures' random permutations were performed to show the empirical p-value distributions...
November 6, 2017: Epigenomics
https://www.readbyqxmd.com/read/29099282/dna-methylation-and-obesity-traits-an-epigenome-wide-association-study-the-regicor-study
#9
Sergi Sayols-Baixeras, Isaac Subirana, Alba Fernández-Sanlés, Mariano Sentí, Carla Lluís-Ganella, Jaume Marrugat, Roberto Elosua
Obesity is associated with increased risk of several diseases and has become epidemic. Obesity is highly heritable but the genetic variants identified by genome-wide association studies explain only limited variability. Epigenetics could contribute to explain the missing variability. The study aim was to discover differential methylation patterns related to obesity. We designed an epigenome-wide association study with a discovery phase in a subsample of 641 REGICOR study participants, validated by analysis of 2,515 participants in the Framingham Offspring Study...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099281/variability-of-genome-wide-dna-methylation-and-mrna-expression-profiles-in-reproductive-and-endocrine-disease-related-tissues
#10
Nilufer Rahmioglu, Alexander W Drong, Helen Lockstone, Thomas Tapmeier, Karin Hellner, Merli Saare, Triin Laisk-Podar, Christine Dew, Emily Tough, George Nicholson, Maire Peters, Andrew P Morris, Cecilia M Lindgren, Christian M Becker, Krina T Zondervan
Genome-wide association studies in the fields of reproductive medicine and endocrinology are yielding robust genetic variants associated with disease. Integrated genomic, transcriptomic, and epigenomic molecular profiling studies are common methodologies used to understand the biological pathways perturbed by these variants. However, molecular profiling resources do not include the tissue most relevant to many female reproductive traits, the endometrium, while the parameters influencing variability of results from its molecular profiling are unclear...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29097680/epigenome-wide-association-studies-identify-dna-methylation-associated-with-kidney-function
#11
Audrey Y Chu, Adrienne Tin, Pascal Schlosser, Yi-An Ko, Chengxiang Qiu, Chen Yao, Roby Joehanes, Morgan E Grams, Liming Liang, Caroline A Gluck, Chunyu Liu, Josef Coresh, Shih-Jen Hwang, Daniel Levy, Eric Boerwinkle, James S Pankow, Qiong Yang, Myriam Fornage, Caroline S Fox, Katalin Susztak, Anna Köttgen
Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/29092026/copd-gwas-variant-at-19q13-2-in-relation-with-dna-methylation-and-gene-expression
#12
Ivana Nedeljkovic, Lies Lahousse, Elena Carnero Montoro, Alen Faiz, Judith M Vonk, Kim de Jong, Diana A van der Plaat, Cleo C van Diemen, Maarten van den Berge, Ma'en Obeidat, Yohan Bossé, David C Nickle, Andre G Uitterlinden, Joyce B J van Meurs, Bruno H C Stricker, Guy G Brusselle, Dirkje S Postma, H Marike Boezen, Cornelia M van Duijn, Najaf Amin
Chronic obstructive pulmonary disease (COPD) is among the major health burdens in adults. While cigarette smoking is the leading risk factor, a growing number of genetic variations have been discovered to influence disease susceptibility. Epigenetic modifications may mediate the response of the genome to smoking and regulate gene expression. Chromosome 19q13.2 region is associated with both smoking and COPD, yet its functional role is unclear. Our study aimed to determine whether rs7937 (RAB4B, EGLN2), a top genetic variant in 19q13...
October 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29082545/testing-for-the-indirect-effect-under-the-null-for-genome-wide-mediation-analyses
#13
Richard Barfield, Jincheng Shen, Allan C Just, Pantel S Vokonas, Joel Schwartz, Andrea A Baccarelli, Tyler J VanderWeele, Xihong Lin
Mediation analysis helps researchers assess whether part or all of an exposure's effect on an outcome is due to an intermediate variable. The indirect effect can help in designing interventions on the mediator as opposed to the exposure and better understanding the outcome's mechanisms. Mediation analysis has seen increased use in genome-wide epidemiological studies to test for an exposure of interest being mediated through a genomic measure such as gene expression or DNA methylation (DNAm). Testing for the indirect effect is challenged by the fact that the null hypothesis is composite...
December 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/29055820/igg-glycosylation-and-dna-methylation-are-interconnected-with-smoking
#14
Annika Wahl, Silva Kasela, Elena Carnero Monotoro, Maarten van Iterson, Jerko Štambuk, Sapna Sharma, Erik van den Akker, Lucija Klaric, Elisa Benedetti, Genadij Razdorov, Irena Trbojević-Akmačić, Frano Vučković, Ivo Ugrina, Marian Beekman, Joris Deelen, Diana van Heemst, Bastiaan T Heijmans, B I O S Consortium, Manfred Wuhrer, Rosina Plomp, Toma Keser, Mirna Šimurina, Tamara Pavić, Ivan Gudelj, Jasminka Krištić, Harald Grallert, Sonja Kunze, Annette Peters, Jordana T Bell, Timothy D Spector, Lili Milani, P Eline Slagboom, Gordan Lauc, Christian Gieger
BACKGROUND: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. METHODS: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies...
October 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29053721/xx-disorder-of-sex-development-is-associated-with-an-insertion-on-chromosome-9-and-downregulation-of-rspo1-in-dogs-canis-lupus-familiaris
#15
Vicki N Meyers-Wallen, Adam R Boyko, Charles G Danko, Jennifer K Grenier, Jason G Mezey, Jessica J Hayward, Laura M Shannon, Chuan Gao, Afrah Shafquat, Edward J Rice, Shashikant Pujar, Stefanie Eggers, Thomas Ohnesorg, Andrew H Sinclair
Remarkable progress has been achieved in understanding the mechanisms controlling sex determination, yet the cause for many Disorders of Sex Development (DSD) remains unknown. Of particular interest is a rare XX DSD subtype in which individuals are negative for SRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both of these phenotypes occur in the same family. This is a naturally occurring disorder in humans (Homo sapiens) and dogs (C. familiaris). Phenotypes in the canine XX DSD model are strikingly similar to those of the human XX DSD subtype...
2017: PloS One
https://www.readbyqxmd.com/read/29047347/the-dynamics-of-smoking-related-disturbed-methylation-a-two-time-point-study-of-methylation-change-in-smokers-non-smokers-and-former-smokers
#16
Rory Wilson, Simone Wahl, Liliane Pfeiffer, Cavin K Ward-Caviness, Sonja Kunze, Anja Kretschmer, Eva Reischl, Annette Peters, Christian Gieger, Melanie Waldenberger
BACKGROUND: The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking...
October 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29046734/epigenome-wide-association-study-of-asthma-and-wheeze-in-childhood-and-adolescence
#17
Ryan Arathimos, Matthew Suderman, Gemma C Sharp, Kimberley Burrows, Raquel Granell, Kate Tilling, Tom R Gaunt, John Henderson, Susan Ring, Rebecca C Richmond, Caroline L Relton
BACKGROUND: Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis. METHODS: Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29036683/cr2cancer-a-database-for-chromatin-regulators-in-human-cancer
#18
Beibei Ru, Jianlong Sun, Yin Tong, Ching Ngar Wong, Aditi Chandra, Acacia Tsz So Tang, Larry Ka Yue Chow, Wai Lam Wun, Zarina Levitskaya, Jiangwen Zhang
Chromatin regulators (CRs) can dynamically modulate chromatin architecture to epigenetically regulate gene expression in response to intrinsic and extrinsic signalling cues. Somatic alterations or misexpression of CRs might reprogram the epigenomic landscape of chromatin, which in turn lead to a wide range of common diseases, notably cancer. Here, we present CR2Cancer, a comprehensive annotation and visualization database for CRs in human cancer constructed by high throughput data analysis and literature mining...
October 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29034560/estimation-of-a-significance-threshold-for-epigenome-wide-association-studies
#19
Ayden Saffari, Matt J Silver, Patrizia Zavattari, Loredana Moi, Amedeo Columbano, Emma L Meaburn, Frank Dudbridge
Epigenome-wide association studies (EWAS) are designed to characterise population-level epigenetic differences across the genome and link them to disease. Most commonly, they assess DNA-methylation status at cytosine-guanine dinucleotide (CpG) sites, using platforms such as the Illumina 450k array that profile a subset of CpGs genome wide. An important challenge in the context of EWAS is determining a significance threshold for declaring a CpG site as differentially methylated, taking multiple testing into account...
October 15, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/29030824/distinguishing-states-of-arrest-genome-wide-descriptions-of-cellular-quiescence-using-chip-seq-and-rna-seq-analysis
#20
Surabhi Srivastava, Hardik P Gala, Rakesh K Mishra, Jyotsna Dhawan
Regenerative potential in adult stem cells is closely associated with the establishment of-and exit from-a temporary state of quiescence. Emerging evidence not only provides a rationale for the link between lineage determination programs and cell cycle regulation but also highlights the understanding of quiescence as an actively maintained cellular program, encompassing networks and mechanisms beyond mitotic inactivity or metabolic restriction. Interrogating the quiescent genome and transcriptome using deep-sequencing technologies offers an unprecedented view of the global mechanisms governing this reversibly arrested cellular state and its importance for cell identity...
2018: Methods in Molecular Biology
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