Association of DNA Methylation Differences With Schizophrenia in an Epigenome-Wide Association Study

Montaño, Carolina; Taub, Margaret A.; Jaffe, Andrew E.; Briem, Eiríkur; Feinberg, Jason I.; Trygvadottir, Rakel; Idrizi, Adrian; Rúnarsson, Árni Rafn; Berndsen, Birna; Gur, Ruben C.; Moore, Tyler M.; Perry, Rodney T.; Fugman, Doug; Sabunciyan, Sarven; Yolken, Robert H.; Hyde, Thomas M.; Kleinman, Joel E.; Sobell, Janet L.; Pato, Carlos N.; Pato, Michele T.; Go, Rodney C.P.; Nimgaonkar, Vishwajit L.; Weinberger, Daniel R.; Braff, David L.; Gur, Raquel E.; Fallin, M. Daniele; Feinberg, Andrew P.

doi:10.1001/jamapsychiatry.2016.0144

Cited by 163 publications

(143 citation statements)

References 70 publications

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“…Similar studies with remarkable findings in the investigation of a variety of diseases as type 2 diabetes mellitus (Soriano-Tarraga et al 2016), psoriasis (Zhou et al 2016), schizophrenia (Montano et al 2016), metabolic syndrome/obesity (Ali et al 2016) and many others have been recently published. It is expected that the new technologies that make possible this type of works and the technologies that will come allow epigenetic epidemiology to reach major objectives as the complete description of the epigenetic processes shaping the development of organisms, the interactions gene-epigene and epigene-environment, the establishment of the role of epigenetics in risk and emergence of diseases, as marker of disease or exposure, and the mechanisms of the inheritance of epigenetic changes over generations in humans (Bollati & Baccarelli 2010;Bakulski & Fallin 2014).…”

Section: Environmental Epigeneticssupporting

confidence: 67%

Epigenetics: from the past to the present

Villota-Salazar

Mendoza‐Mendoza

González-Prieto

2016

Frontiers in Life Science

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The definition of epigenetics is still under intense debate; however, its concept has evolved since it was originally introduced in 1939 by Conrad Hal Waddington as a way to reconcile antagonistic views between the school of preformationism and the school of epigenesis. The characterization of a large number of phenomena that diverge from the dogmas of classical genetics, and the discovery of the molecular mechanisms through which these phenomena occur, has given rise to a new area of study with important implications for biological sciences. Interactions between the environment and the DNA through modifications on the chromatin are not only responsible for the expression of a normal phenotype, these may be involved in the development of various pathologies. The epigenome, as the bridge between the genome and the phenotype, is no doubt one of the most interesting current ideas in genetics and is so revolutionary that it may change our present notions about inheritance and evolution. In this review, we made a compilation of the most important events in the history of epigenetics, its implications and some perspectives to the future.

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Section: Environmental Epigeneticssupporting

confidence: 67%

Epigenetics: from the past to the present

Villota-Salazar

Mendoza‐Mendoza

González-Prieto

2016

Frontiers in Life Science

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“…This gene encodes a transcription factor that regulates TGF-β signaling and is mutated in nearly 90% of cases of ShprintzenGoldberg syndrome (OMIM #182212), a condition entailing craniofacial and brain anomalies [Au et al, 2014]. This gene is found to be methylated in SZ patients [Montano et al, 2016]. Indeed, in the brain, SKI regulates the proliferation and differentiation of neural precursors, along with the specification of cortical projections [Lyons et al, 1994;Baranek and Atanasoski, 2012].…”

Section: Functional Implication and Biological Interpretation Of Domementioning

confidence: 99%

“…4 a) possibly indicative of an impaired glial function. Indeed, SKI methylation has been described in SZ brains [Montano et al, 2016].…”

Section: Functional Implication and Biological Interpretation Of Domementioning

confidence: 99%

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

et al. 2017

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Schizophrenia (SZ) is a pervasive neurodevelopmental disorder that entails social and cognitive deficits, including marked language problems. Its complex multifactorial etiopathogenesis, including genetic and environmental factors, is still widely uncertain. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, for unclear reasons. It has been hypothesized that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history, and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this hypothesis, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our behavior and cognition, and to favor the emergence of complex languages through cultural evolution. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from the hypofunction of the neural crest. It is our intention to show that people with SZ exhibit more marked domesticated traits at the morphological, physiological, and behavioral levels. We also show that genes involved in domestication and neural crest development and function comprise nearly 20% of SZ candidates, most of which exhibit altered expression profiles in the brain of SZ patients, specifically in areas involved in language processing. Based on these observations, we conclude that SZ may represent an abnormal ontogenetic itinerary for the human faculty of language, resulting, at least in part, from changes in genes important for the domestication syndrome and primarily involving the neural crest.

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“…Much of the work toward epigenetically characterizing the schizophrenia epigenome has involved measuring direct DNA methylation through bisulphite sequencing and similar methods. For example, a recent study (41 cases, 46 controls) across 4 brain regions found many genome regions that displayed differentially methylated DNA [28], while a larger study (689 cases, 645 controls) using blood samples similarly identified many differentially methylated loci [29]. Other studies support the importance of DNA cytosine methylation in schizophrenia [30-32].…”

Section: Mechanisms Of Epigenetic Regulationmentioning

confidence: 99%

Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches

et al. 2019

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Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable component, few individual loci have been identified in genomewide screens, suggesting a role for epigenetic effects. Rather, large numbers of weakly acting loci may cumulatively increase disease risk, including several mapping to epigenetic pathways. In this review, we discuss mechanisms of epigenetic regulation and evidence for an epigenetic contribution to disease phenotype. We further describe the range of experimental tools currently available to study epigenetic effects associated with the disease.

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Association of DNA Methylation Differences With Schizophrenia in an Epigenome-Wide Association Study

Cited by 163 publications

References 70 publications

Epigenetics: from the past to the present

Epigenetics: from the past to the present

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches

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