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Epigenome wide association

Rebecca C Richmond, Gemma C Sharp, Georgia Herbert, Charlotte Atkinson, Caroline Taylor, Sohinee Bhattacharya, Doris Campbell, Marion Hall, Nabila Kazmi, Tom Gaunt, Wendy McArdle, Susan Ring, George Davey Smith, Andy Ness, Caroline L Relton
Background: It has been proposed that maternal folic-acid supplement use may alter the DNA-methylation patterns of the offspring during the in-utero period, which could influence development and later-life health outcomes. Evidence from human studies suggests a role for prenatal folate levels in influencing DNA methylation in early life, but this has not been extended to consider persistent effects into adulthood. Methods: To better elucidate the long-term impact of maternal folic acid in pregnancy on DNA methylation in offspring, we carried out an epigenome-wide association study (EWAS) nested within the Aberdeen Folic Acid Supplementation Trial (AFAST-a trial of two different doses: 0...
March 12, 2018: International Journal of Epidemiology
Raphaël Mourad, Krzysztof Ginalski, Gaëlle Legube, Olivier Cuvier
Double-strand breaks (DSBs) result from the attack of both DNA strands by multiple sources, including radiation and chemicals. DSBs can cause the abnormal chromosomal rearrangements associated with cancer. Recent techniques allow the genome-wide mapping of DSBs at high resolution, enabling the comprehensive study of their origins. However, these techniques are costly and challenging. Hence, we devise a computational approach to predict DSBs using the epigenomic and chromatin context, for which public data are readily available from the ENCODE project...
March 15, 2018: Genome Biology
Ryu Miura, Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Sachiko Kobayashi, Shu-Li Wang, Chung-Hsing Chen, Kunio Miyake, Mayumi Ishizuka, Yusuke Iwasaki, Yoichi M Ito, Takeo Kubota, Reiko Kishi
BACKGROUND: Prenatal exposure to perfluoroalkyl substances (PFASs) influences fetal development and later in life. OBJECTIVE: To investigate cord blood DNA methylation changes associated with prenatal exposure to PFASs. METHODS: We assessed DNA methylation in cord blood samples from 190 mother-child pairs from the Sapporo cohort of the Hokkaido Study (discovery cohort) and from 37 mother-child pairs from the Taiwan Maternal and Infant Cohort Study (replication cohort) using the Illumina HumanMethylation 450 BeadChip...
March 12, 2018: Environment International
Yunfeng Huang, Qin Hui, Douglas I Walker, Karan Uppal, Jack Goldberg, Dean P Jones, Viola Vaccarino, Yan V Sun
AIM: We conducted a joint metabolomic-epigenomic study to identify patterns of epigenetic associations with smoking-related metabolites. PATIENTS & METHODS: We performed an untargeted metabolome-wide association study of smoking and epigenome-wide association studies of smoking-related metabolites among 180 male twins. We examined the patterns of epigenetic association linked to smoking-related metabolites using hierarchical clustering. RESULTS: Among 12 annotated smoking-related metabolites identified from a metabolome-wide association study, we observed significant hypomethylation associated with increased level of N-acetylpyrrolidine, cotinine, 5-hydroxycotinine and nicotine and hypermethylation associated with increased level of 8-oxoguanine...
March 12, 2018: Epigenomics
Qijun Cheng, Bin Zhao, Zhenxiang Huang, Yanhua Su, Biqin Chen, Songjing Yang, Xueqi Peng, Qilin Ma, Xiaoshan Yu, Benhua Zhao, Xiayi Ke
BACKGROUND & AIM: Hepatitis B virus (HBV) can be transmitted to infants, and is related to infants' later disease risk. Epigenetic change (such as DNA methylation) may be mechanism underlying the relationship. In this study, we aimed to investigate whether prenatal HBV infection could alter DNA methylation status in newborns. METHOD: We selected 12 neonates with intrauterine HBV infection whose mothers were HBsAg-positive during pregnancy, relative to 12 HBV-free neonates with HBsAg-negative mothers...
March 8, 2018: Gene
Magali Kernaleguen, Christian Daviaud, Yimin Shen, Eric Bonnet, Victor Renault, Jean-François Deleuze, Florence Mauger, Jörg Tost
The analysis of genome-wide epigenomic alterations including DNA methylation and hydroxymethylation has become a subject of intensive research for many biological and disease-associated investigations. Whole-genome bisulfite sequencing (WGBS) using next-generation sequencing technologies is currently considered as the gold standard for a comprehensive and quantitative analysis of DNA methylation throughout the genome. However, bisulfite conversion does not allow distinguishing between cytosine methylation and hydroxymethylation requiring an additional chemical or enzymatic step to identify hydroxymethylated cytosines...
2018: Methods in Molecular Biology
Shlomo Yeshurun, Anthony J Hannan
In recent years, striking new evidence has demonstrated non-genetic inheritance of acquired traits associated with parental environmental exposures. In particular, this transgenerational modulation of phenotypic traits is of direct relevance to psychiatric disorders, including depression, post-traumatic stress disorder, and other anxiety disorders. Here we review the recent progress in this field, with an emphasis on acquired traits of psychiatric illnesses transmitted epigenetically via the male lineage. We discuss the transgenerational effects of paternal exposure to stress vs...
March 8, 2018: Molecular Psychiatry
Kirstin Mittelstraß, Melanie Waldenberger
PURPOSE OF REVIEW: It is becoming increasingly evident that epigenetic mechanisms, particularly DNA methylation, play a role in the regulation of blood lipid levels and lipid metabolism-linked phenotypes and diseases. RECENT FINDINGS: Recent genome-wide methylation and candidate gene studies of blood lipids have highlighted several robustly replicated methylation markers across different ethnicities. Furthermore, many of these lipid-related CpG sites associated with blood lipids are also linked to lipid-related phenotypes and diseases...
April 2018: Current Opinion in Lipidology
Robert-Jan Palstra, Elisa de Crignis, Michael D Röling, Thomas van Staveren, Tsung Wai Kan, Wilfred van Ijcken, Yvonne M Mueller, Peter D Katsikis, Tokameh Mahmoudi
We integrated data obtained from HIV-1 genome-wide association studies with T cell-derived epigenome data and found that the noncoding intergenic variant rs4349147, which is statistically associated with HIV-1 acquisition, is located in a CD4+ T cell-specific deoxyribonuclease I hypersensitive region, suggesting regulatory potential for this variant. Deletion of the rs4349147 element in Jurkat cells strongly reduced expression of interleukin-32 (IL-32), approximately 10-kb upstream, and chromosome conformation capture assays identified a chromatin loop between rs4349147 and the IL-32 promoter validating its function as a long-distance enhancer...
February 2018: Science Advances
Mario Bauer
Background: Both genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are aiming to discover molecular signs for diseases, which possibly can be helpful for future therapeutic intervention strategies. The most prominently used tissue in association studies on humans is venous blood. In contrast to the unchangeable genotype, epigenetic DNA methylation is more variable. Methylation is affected not only by a subject's constitution such as age, gender, ethnicity, genotype, lifestyle and health status, but is also determined by tissue-specific cell types...
March 1, 2018: International Journal of Epidemiology
Sabine A Fraschka, Michael Filarsky, Regina Hoo, Igor Niederwieser, Xue Yan Yam, Nicolas M B Brancucci, Franziska Mohring, Annals T Mushunje, Ximei Huang, Peter R Christensen, Francois Nosten, Zbynek Bozdech, Bruce Russell, Robert W Moon, Matthias Marti, Peter R Preiser, Richárd Bártfai, Till S Voss
Heterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential...
February 22, 2018: Cell Host & Microbe
Kimberley J Billingsley, Maurizio Manca, Olympia Gianfrancesco, David A Collier, Helen Sharp, Vivien J Bubb, John P Quinn
Genomic wide association studies identified the CACNA1C locus as genetically associated with both schizophrenia and bipolar affective disorder. CACNA1C encodes Cav1.2, one of four subunits of L-type voltage gated calcium channels. Variation resides in non-coding regions of CACNA1C which interact with the promoter and are validated expression quantitative trait loci. Using reporter gene constructs we demonstrate the CACNA1C promoter is a major mediator of inducible regulation of CACNA1C activity in the SH-SY5Y neuroblastoma cell line...
February 28, 2018: Schizophrenia Research
Carl Baribault, Kenneth C Ehrlich, V K Chaithanya Ponnaluri, Sriharsa Pradhan, Michelle Lacey, Melanie Ehrlich
DNA methylation can affect tissue-specific gene transcription in ways that are difficult to discern from studies focused on genome-wide analyses of differentially methylated regions (DMRs). To elucidate the variety of associations between differentiation-related DNA hypermethylation and transcription, we used available epigenomic and transcriptomic profiles from 38 human cell/tissue types to focus on such relationships in 94 genes linked to hypermethylated DMRs in myoblasts (Mb). For 19 of the genes, promoter-region hypermethylation in Mb (and often a few heterologous cell types) was associated with gene repression but, importantly, DNA hypermethylation was absent in many other repressed samples...
March 2, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Cheng-Jian Xu, Cilla Söderhäll, Mariona Bustamante, Nour Baïz, Olena Gruzieva, Ulrike Gehring, Dan Mason, Leda Chatzi, Mikel Basterrechea, Sabrina Llop, Maties Torrent, Francesco Forastiere, Maria Pia Fantini, Karin C Lødrup Carlsen, Tari Haahtela, Andréanne Morin, Marjan Kerkhof, Simon Kebede Merid, Bianca van Rijkom, Soesma A Jankipersadsing, Marc Jan Bonder, Stephane Ballereau, Cornelis J Vermeulen, Raul Aguirre-Gamboa, Johan C de Jongste, Henriette A Smit, Ashish Kumar, Göran Pershagen, Stefano Guerra, Judith Garcia-Aymerich, Dario Greco, Lovisa Reinius, Rosemary R C McEachan, Raf Azad, Vegard Hovland, Petter Mowinckel, Harri Alenius, Nanna Fyhrquist, Nathanaël Lemonnier, Johann Pellet, Charles Auffray, Pieter van der Vlies, Cleo C van Diemen, Yang Li, Cisca Wijmenga, Mihai G Netea, Miriam F Moffatt, William O C M Cookson, Josep M Anto, Jean Bousquet, Tiina Laatikainen, Catherine Laprise, Kai-Håkon Carlsen, Davide Gori, Daniela Porta, Carmen Iñiguez, Jose Ramon Bilbao, Manolis Kogevinas, John Wright, Bert Brunekreef, Juha Kere, Martijn C Nawijn, Isabella Annesi-Maesano, Jordi Sunyer, Erik Melén, Gerard H Koppelman
BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design...
February 26, 2018: Lancet Respiratory Medicine
Cajsa Davegårdh, Sonia García-Calzón, Karl Bacos, Charlotte Ling
BACKGROUND: Type 2 diabetes (T2D) is a multifactorial, polygenic disease caused by impaired insulin secretion and insulin resistance. Genome-wide association studies (GWAS) were expected to resolve a large part of the genetic component of diabetes; yet, the single nucleotide polymorphisms identified by GWAS explain less than 20% of the estimated heritability for T2D. There was subsequently a need to look elsewhere to find disease-causing factors. Mechanisms mediating the interaction between environmental factors and the genome, such as epigenetics, may be of particular importance in the pathogenesis of T2D...
February 7, 2018: Molecular Metabolism
Ralph Stadhouders, Bobby W S Li, Marjolein J W de Bruijn, Antonio Gomez, Tata Nageswara Rao, Hans Jörg Fehling, Wilfred F J van IJcken, Ai Ing Lim, James P Di Santo, Thomas Graf, Rudi W Hendriks
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are major producers of cytokines driving allergic asthma and elevated numbers of ILC2s have been detected in blood and sputum of asthma patients. Asthma susceptibility has a strong genetic component, but the underlying mechanisms and whether asthma genetics impact ILC2 biology remains unclear. OBJECTIVE: To study the ILC2 transcriptome and epigenome during airway inflammation (AI) in order to couple these to genes and genetic variants associated with asthma pathogenesis...
February 24, 2018: Journal of Allergy and Clinical Immunology
Namitha Mohandas, Sebastian Bass-Stringer, Jovana Maksimovic, Kylie Crompton, Yuk J Loke, Janet Walstab, Susan M Reid, David J Amor, Dinah Reddihough, Jeffrey M Craig
Background: Cerebral palsy (CP) is a clinical description for a group of motor disorders that are heterogeneous with respect to causes, symptoms and severity. A diagnosis of CP cannot usually be made at birth and in some cases may be delayed until 2-3 years of age. This limits opportunities for early intervention that could otherwise improve long-term outcomes. CP has been recorded in monozygotic twins discordant for the disorder, indicating a potential role of non-genetic factors such as intrauterine infection, hypoxia-ischaemia, haemorrhage and thrombosis...
2018: Clinical Epigenetics
Edward D Barker
Epigenetic modification, such as DNA methylation (DNAm), is a mechanism that can help explain how early adversities can engender long-term vulnerability for mental health problems. At present, there is preliminary evidence to support the possibility of epigenetic mediation: environmental factors are reported to influence offspring DNAm, which in turn associate with child and adolescent psychopathology. However, all analyses have been correlational in nature and, as these studies have focussed on children and adolescents, DNAm has been based on peripheral tissue (cord blood, whole blood, buccal cells)...
February 23, 2018: Psychopathology
Agatha Schlüter, Juan Sandoval, Stéphane Fourcade, Angel Díaz-Lagares, Montserrat Ruiz, Patrizia Casaccia, Manel Esteller, Aurora Pujol
Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN). All patients harbor loss of function mutations in the ABCD1 peroxisomal transporter of very-long chain fatty acids...
February 24, 2018: Brain Pathology
Ying Wang, Xiaoxi Huang, Dong Leng, Jifeng Li, Lei Wang, Yan Liang, Jun Wang, Ran Miao, Tao Jiang
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease which is often underpinned by vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling, their biological role in CTEPH is not entirely clear. In this study, we analyzed the whole epigenome-wide DNA methylation profiles of cultured PASMCs from CTEPH and control cell lines using an Illumina HumanMethylation450K BeadChip. A total of 6829 significantly differentially methylated probes (DMPs) were detected between the two groups, of which 4246 DMPs were hypermethylated while 2583 DMPs were hypomethylated...
February 23, 2018: Physiological Genomics
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