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Schizophrenia Epigenetics

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https://www.readbyqxmd.com/read/29579179/a-bayesian-framework-for-multiple-trait-colo-calization-from-summary-association-statistics
#1
Claudia Giambartolomei, Jimmy Zhenli Liu, Wen Zhang, Mads Hauberg, Huwenbo Shi, James Boocock, Joe Pickrell, Andrew E Jaffe, Bogdan Pasaniuc, Panos Roussos
Motivation: Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk...
March 19, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29573791/understanding-the-molecular-mechanisms-underpinning-gene-by-environment-interactions-in-psychiatric-disorders-the-fkbp5-model
#2
REVIEW
Natalie Matosin, Thorhildur Halldorsdottir, Elisabeth B Binder
Epidemiologic and genetic studies suggest common environmental and genetic risk factors for a number of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Genetic and environmental factors, especially adverse life events, not only have main effects on disease development but also may interact to shape risk and resilience. Such gene by adversity interactions have been described for FKBP5, an endogenous regulator of the stress-neuroendocrine system, conferring risk for a number of psychiatric disorders...
March 21, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29565038/gabaergic-inhibitory-neurons-as-therapeutic-targets-for-cognitive-impairment-in-schizophrenia
#3
REVIEW
Meng-Yi Xu, Albert H C Wong
Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing...
March 22, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29555928/altered-dna-methylation-associated-with-a-translocation-linked-to-major-mental-illness
#4
Daniel L McCartney, Rosie M Walker, Stewart W Morris, Susan M Anderson, Barbara J Duff, Riccardo E Marioni, J Kirsty Millar, Shane E McCarthy, Niamh M Ryan, Stephen M Lawrie, Andrew R Watson, Douglas H R Blackwood, Pippa A Thomson, Andrew M McIntosh, W Richard McCombie, David J Porteous, Kathryn L Evans
Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA)...
March 19, 2018: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29540737/g-protein-coupled-receptor-gpr17-regulates-oligodendrocyte-differentiation-in-response-to-lysolecithin-induced-demyelination
#5
Changqing Lu, Lihua Dong, Hui Zhou, Qianmei Li, Guojiao Huang, Shu Jun Bai, Linchuan Liao
Oligodendrocytes are the myelin-producing cells of the central nervous system (CNS). A variety of brain disorders from "classical" demyelinating diseases, such as multiple sclerosis, stroke, schizophrenia, depression, Down syndrome and autism, are shown myelination defects. Oligodendrocyte myelination is regulated by a complex interplay of intrinsic, epigenetic and extrinsic factors. Gpr17 (G protein-coupled receptor 17) is a G protein-coupled receptor, and has been identified to be a regulator for oligodendrocyte development...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29529098/validation-of-a-microrna-target-site-polymorphism-in-h3f3b-that-is-potentially-associated-with-a-broad-schizophrenia-phenotype
#6
William Manley, Michael P Moreau, Marco Azaro, Stephen K Siecinski, Gillian Davis, Steven Buyske, Veronica Vieland, Anne S Bassett, Linda Brzustowicz
Despite much progress, few genetic findings for schizophrenia have been assessed by functional validation experiments at the molecular level. We previously reported evidence for genetic linkage of broadly defined schizophrenia to chromosome 17q25 in a sample of 24 multiplex families. 2,002 SNPs under this linkage peak were analyzed for evidence of linkage disequilibrium using the posterior probability of linkage (PPL) framework. SNP rs1060120 produced the strongest evidence for association, with a PPLD|L score of 0...
2018: PloS One
https://www.readbyqxmd.com/read/29524155/reproductive-genetics-and-the-aging-male
#7
REVIEW
Alexander N Yatsenko, Paul J Turek
PURPOSE: To examine current evidence of the known effects of advanced paternal age on sperm genetic and epigenetic changes and associated birth defects and diseases in offspring. METHODS: Review of published PubMed literature. RESULTS: Advanced paternal age (> 40 years) is associated with accumulated damage to sperm DNA and mitotic and meiotic quality control mechanisms (mismatch repair) during spermatogenesis. This in turn causes well-delineated abnormalities in sperm chromosomes, both numerical and structural, and increased sperm DNA fragmentation (3%/year of age) and single gene mutations (relative risk, RR 10)...
March 9, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29512462/dysfunction-in-brain-derived-neurotrophic-factor-signaling-pathway-and-susceptibility-to-schizophrenia-parkinson-s-and-alzheimer-s-diseases
#8
Alireza Mohammadi, Vahid Ghasem Amooeian, Ehsan Rashidi
Brain-derived neurotrophic factor (BDNF) is a dominant neurotrophic factor in the brain which plays a crucial role in differentiation, regeneration and plasticity mechanisms. Binding of the BDNF to its high-affinity tropomyosin-related kinase B (TrkB) receptor leads to phosphorylation of TrkB, thus activating the three important downstream intracellular signaling cascades within the neural cells including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), phospholipase C-γ (PLCγ), and mitogen-activated protein kinase/extracellular signal related kinase (MAPK/ERK) pathways...
March 2, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29499474/dna-methylation-of-ankk1-and-response-to-aripiprazole-in-patients-with-acute-schizophrenia-a-preliminary-study
#9
Itaru Miura, Yasuto Kunii, Mizuki Hino, Hiroshi Hoshino, Junya Matsumoto, Keiko Kanno-Nozaki, Sho Horikoshi, Haruka Kaneko, Miki Bundo, Kazuya Iwamoto, Hirooki Yabe
Epigenetic modification including DNA methylation may affect pathophysiology and the response to antipsychotic drugs in patients with schizophrenia. The objective of the present study was to investigate the effect of the DNA methylation of ANKK1 (ankyrin repeat and kinase domain containing 1) on the response to aripiprazole and plasma levels of monoamine metabolites in antipsychotic-free acute schizophrenia patients. The subjects were 34 Japanese patients with schizophrenia who had been treated with aripiprazole for 6 weeks...
February 23, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29482655/characterization-of-cross-tissue-genetic-epigenetic-effects-and-their-patterns-in-schizophrenia
#10
Dongdong Lin, Jiayu Chen, Nora Perrone-Bizzozero, Juan R Bustillo, Yuhui Du, Vince D Calhoun, Jingyu Liu
BACKGROUND: One of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders...
February 26, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29463818/changed-frontal-pole-gene-expression-suggest-altered-interplay-between-neurotransmitter-developmental-and-inflammatory-pathways-in-schizophrenia
#11
Elizabeth Scarr, Madhara Udawela, Brian Dean
Schizophrenia (Sz) probably occurs after genetically susceptible individuals encounter a deleterious environmental factor that triggers epigenetic mechanisms to change CNS gene expression. To determine if omnibus changes in CNS gene expression are present in Sz, we compared mRNA levels in the frontal pole (Brodmann's area (BA) 10), the dorsolateral prefrontal cortex (BA 9) and cingulate cortex (BA 33) from 15 subjects with Sz and 15 controls using the Affymetrix™ Human Exon 1.0 ST Array. Differences in mRNA levels (±≥20%; p < 0...
February 20, 2018: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29448178/modification-of-the-association-between-antipsychotic-treatment-response-and-childhood-adversity-by-mmp9-gene-variants-in-a-first-episode-schizophrenia-cohort
#12
Nathaniel McGregor, Nicole Thompson, Kevin Sean O'Connell, Robin Emsley, Lize van der Merwe, Louise Warnich
Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity...
February 7, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29435496/zika-virus-alters-dna-methylation-of-neural-genes-in-an-organoid-model-of-the-developing-human-brain
#13
Sylvie Janssens, Michael Schotsaert, Rahul Karnik, Vinod Balasubramaniam, Marion Dejosez, Alexander Meissner, Adolfo García-Sastre, Thomas P Zwaka
Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia...
January 2018: MSystems
https://www.readbyqxmd.com/read/29430824/dna-methylation-analyses-of-the-candidate-genes-identified-by-a-methylome-wide-association-study-revealed-common-epigenetic-alterations-in-schizophrenia-and-bipolar-disorder
#14
Hiroko Sugawara, Yui Murata, Tempei Ikegame, Rie Sawamura, Shota Shimanaga, Yusuke Takeoka, Takeo Saito, Masashi Ikeda, Akane Yoshikawa, Fumichika Nishimura, Yoshiya Kawamura, Chihiro Kakiuchi, Tsukasa Sasaki, Nakao Iwata, Mamoru Hashimoto, Kiyoto Kasai, Tadafumi Kato, Miki Bundo, Kazuya Iwamoto
AIM: Schizophrenia (SZ) and bipolar disorder (BD) have been known to share genetic and environmental risk factors, and complex gene-environmental interactions may contribute to their pathophysiology. In contrast to high genetic overlap between SZ and BD, as revealed by genome-wide association studies, the extent of epigenetic overlap remains largely unknown. In the present study, we explore if SZ and BD share epigenetic risk factors in the same manner as they share genetic components...
February 11, 2018: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29417943/inhibition-of-the-g9a-glp-histone-methyltransferase-complex-modulates-anxiety-related-behavior-in-mice
#15
Dong-Yao Wang, Joel Kosowan, James Samsom, Laura Leung, Kai-Lai Zhang, Ying-Xiang Li, Yan Xiong, Jian Jin, Arturas Petronis, Gabriel Oh, Albert H C Wong
Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Two proteins, G9a (also known as EHMT2 or KMT1C) and GLP (G9a-like protein, also known as EHMT1 or KMT1D), which methylate lysine 9 of histone H3 (H3K9), could be promising anxiolytic targets...
February 8, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29383983/the-role-of-the-gut-microbiota-in-schizophrenia-current-and-future-perspectives
#16
Daniela Rodrigues-Amorim, Tania Rivera-Baltanás, Benito Regueiro, Carlos Spuch, María Elena de Las Heras, Raul Váquez-Noguerol Méndez, Maria Nieto-Araujo, C Barreiro-Villar, Jose M Olivares, Roberto C Agís-Balboa
OBJECTIVES: Schizophrenia is a poorly understood chronic disease. Its pathophysiology is complex, dynamic, and linked to epigenetic mechanisms and microbiota involvement. Nowadays, correlating schizophrenia with the environment makes sense owing, to its multidimensional implications: temporal and spatial variability. Microbiota involvement and epigenetic mechanisms are factors that are currently being considered to better understand another dimension of schizophrenia. METHODS: This review summarizes and discusses currently available information, focusing on the microbiota, epigenetic mechanisms, technological approaches aimed at performing exhaustive analyses of the microbiota, and psychotherapies, to establish future perspectives...
January 31, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29382824/genetic-estimators-of-dna-methylation-provide-insights-into-the-molecular-basis-of-polygenic-traits
#17
Virginie Freytag, Vanja Vukojevic, Holger Wagner-Thelen, Annette Milnik, Christian Vogler, Markus Leber, Leonie Weinhold, Anne C Böhmer, Steffi Riedel-Heller, Wolfgang Maier, Dominique J-F de Quervain, Alfredo Ramirez, Andreas Papassotiropoulos
The large biological distance between genetic risk loci and their mechanistic consequences in the tissue of interest limits the ability to establish functionality of susceptibility variants for genetically complex traits. Such a biological gap may be reduced through the systematic study of molecular mediators of genomic action, such as epigenetic modification. Here, we report the identification of robust genetic estimators of whole-blood CpG methylation, which can serve as intermediate molecular traits amenable to association testing with other genetically complex traits...
January 31, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29364120/adaptive-sparse-multiple-canonical-correlation-analysis-with-application-to-imaging-epi-genomics-study-of-schizophrenia
#18
Wenxing Hu, Dongdong Lin, Shaolong Cao, Jingyu Liu, Jiayu Chen, Vince D Calhoun, Yu-Ping Wang
Finding correlations across multiple data sets in imaging and (epi)genomics is a common challenge. Sparse multiple canonical correlation analysis (SMCCA) is a multivariate model widely used to extract contributing features from each data while maximizing the cross-modality correlation. The model is achieved by using the combination of pairwise covariances between any two data sets. However, the scales of different pairwise covariances could be quite different and the direct combination of pairwise covariances in SMCCA is unfair...
February 2018: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/29357805/protein-c-reactive-as-biomarker-predictor-of-schizophrenia-phases-of-illness-a-systematic-review
#19
Laura Orsolini, Fabiola Sarchione, Federica Vellante, Michele Fornaro, Ilaria Matarazzo, Giovanni Martinotti, Alessandro Valchera, Marco Di Nicola, Alessandro Carano, Massimo Di Giannantonio, Giampaolo Perna, Luigi Olivieri, Domenico De Berardis
BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible of the schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well supposed. Accordingly, it has been recently investigated the role of an acute inflammatory phase protein, the C-reactive protein (CRP)...
January 19, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29343074/understanding-the-influence-of-antipsychotic-drugs-on-global-methylation-events-and-its-relevance-in-treatment-response
#20
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response. METHODS: Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs...
January 18, 2018: Epigenomics
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