Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms
Identifieur interne : 004A16 ( Pmc/Curation ); précédent : 004A15; suivant : 004A17Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms
Auteurs : Sylvie Tordjman [France] ; Eszter Somogyi [France] ; Nathalie Coulon [France] ; Solenn Kermarrec [France] ; David Cohen [France] ; Guillaume Bronsard [France] ; Olivier Bonnot [France] ; Catherine Weismann-Arcache [France] ; Michel Botbol [France] ; Bertrand Lauth [Islande] ; Vincent Ginchat [France] ; Pierre Roubertoux [France] ; Marianne Barburoth [France] ; Viviane Kovess [France] ; Marie-Maude Geoffray [France] ; Jean Xavier [France]Source :
- Frontiers in Psychiatry [ 1664-0640 ] ; 2014.
Abstract
Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal, and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene × environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of
Url:
DOI: 10.3389/fpsyt.2014.00053
PubMed: 25136320
PubMed Central: 4120683
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms</title>
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<author><name sortKey="Cohen, David" sort="Cohen, David" uniqKey="Cohen D" first="David" last="Cohen">David Cohen</name>
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<author><name sortKey="Bronsard, Guillaume" sort="Bronsard, Guillaume" uniqKey="Bronsard G" first="Guillaume" last="Bronsard">Guillaume Bronsard</name>
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<author><name sortKey="Bonnot, Olivier" sort="Bonnot, Olivier" uniqKey="Bonnot O" first="Olivier" last="Bonnot">Olivier Bonnot</name>
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<author><name sortKey="Weismann Arcache, Catherine" sort="Weismann Arcache, Catherine" uniqKey="Weismann Arcache C" first="Catherine" last="Weismann-Arcache">Catherine Weismann-Arcache</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Lauth, Bertrand" sort="Lauth, Bertrand" uniqKey="Lauth B" first="Bertrand" last="Lauth">Bertrand Lauth</name>
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<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Roubertoux, Pierre" sort="Roubertoux, Pierre" uniqKey="Roubertoux P" first="Pierre" last="Roubertoux">Pierre Roubertoux</name>
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,<addr-line>Marseille</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Barburoth, Marianne" sort="Barburoth, Marianne" uniqKey="Barburoth M" first="Marianne" last="Barburoth">Marianne Barburoth</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Kovess, Viviane" sort="Kovess, Viviane" uniqKey="Kovess V" first="Viviane" last="Kovess">Viviane Kovess</name>
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,<addr-line>Paris</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Geoffray, Marie Maude" sort="Geoffray, Marie Maude" uniqKey="Geoffray M" first="Marie-Maude" last="Geoffray">Marie-Maude Geoffray</name>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Service Universitaire de Psychiatrie de l’Enfant et de l’Adolescent Hospitalier Le Vinatier</institution>
,<addr-line>Bron</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Xavier, Jean" sort="Xavier, Jean" uniqKey="Xavier J" first="Jean" last="Xavier">Jean Xavier</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Child and Adolescent Psychiatry, AP-HP, GH Pitié-Salpétrière, CNRS FRE 2987, University Pierre and Marie Curie</institution>
,<addr-line>Paris</addr-line>
,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<series><title level="j">Frontiers in Psychiatry</title>
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<front><div type="abstract" xml:lang="en"><p>Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal, and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene × environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of <italic>in utero</italic>
exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention, and early therapeutic intervention of ASD.</p>
</div>
</front>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Psychiatry</journal-id>
<journal-id journal-id-type="iso-abbrev">Front Psychiatry</journal-id>
<journal-id journal-id-type="publisher-id">Front. Psychiatry</journal-id>
<journal-title-group><journal-title>Frontiers in Psychiatry</journal-title>
</journal-title-group>
<issn pub-type="epub">1664-0640</issn>
<publisher><publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25136320</article-id>
<article-id pub-id-type="pmc">4120683</article-id>
<article-id pub-id-type="doi">10.3389/fpsyt.2014.00053</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Psychiatry</subject>
<subj-group><subject>Review Article</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Tordjman</surname>
<given-names>Sylvie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/83064"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Somogyi</surname>
<given-names>Eszter</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/118327"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Coulon</surname>
<given-names>Nathalie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kermarrec</surname>
<given-names>Solenn</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cohen</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/102560"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Bronsard</surname>
<given-names>Guillaume</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bonnot</surname>
<given-names>Olivier</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weismann-Arcache</surname>
<given-names>Catherine</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Botbol</surname>
<given-names>Michel</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/131101"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Lauth</surname>
<given-names>Bertrand</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ginchat</surname>
<given-names>Vincent</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Roubertoux</surname>
<given-names>Pierre</given-names>
</name>
<xref ref-type="aff" rid="aff8"><sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Barburoth</surname>
<given-names>Marianne</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/94976"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Kovess</surname>
<given-names>Viviane</given-names>
</name>
<xref ref-type="aff" rid="aff9"><sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Geoffray</surname>
<given-names>Marie-Maude</given-names>
</name>
<xref ref-type="aff" rid="aff10"><sup>10</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/144176"></uri>
</contrib>
<contrib contrib-type="author"><name><surname>Xavier</surname>
<given-names>Jean</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/107117"></uri>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup>
<institution>Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158</institution>
,<addr-line>Paris</addr-line>
,<country>France</country>
</aff>
<aff id="aff2"><sup>2</sup>
<institution>Pôle Hospitalo-Universitaire de Psychiatrie de l’Enfant et de l’Adolescent, Université de Rennes 1, Centre Hospitalier Guillaume Régnier</institution>
,<addr-line>Rennes</addr-line>
,<country>France</country>
</aff>
<aff id="aff3"><sup>3</sup>
<institution>Department of Child and Adolescent Psychiatry, AP-HP, GH Pitié-Salpétrière, CNRS FRE 2987, University Pierre and Marie Curie</institution>
,<addr-line>Paris</addr-line>
,<country>France</country>
</aff>
<aff id="aff4"><sup>4</sup>
<institution>Laboratoire de Santé Publique (EA3279), School of Medicine of La Timone</institution>
,<addr-line>Marseille</addr-line>
,<country>France</country>
</aff>
<aff id="aff5"><sup>5</sup>
<institution>Laboratoire Psychologie et Neurosciences de la Cognition et de l’Affectivité, Université de Rouen</institution>
,<addr-line>Mont Saint Aignan</addr-line>
,<country>France</country>
</aff>
<aff id="aff6"><sup>6</sup>
<institution>Service Hospitalo-Universitaire de Psychiatrie de l’Enfant et de l’Adolescent, Université de Bretagne Occidentale, CHU de Brest</institution>
,<addr-line>Brest</addr-line>
,<country>France</country>
</aff>
<aff id="aff7"><sup>7</sup>
<institution>Department of Child and Adolescent Psychiatry, Landspitali University Hospital, University of Iceland</institution>
,<addr-line>Reykjavik</addr-line>
,<country>Iceland</country>
</aff>
<aff id="aff8"><sup>8</sup>
<institution>Laboratoire de Génétique Médicale, Génomique Fonctionnelle, INSERM U 910, Université d’Aix-Marseille 2</institution>
,<addr-line>Marseille</addr-line>
,<country>France</country>
</aff>
<aff id="aff9"><sup>9</sup>
<institution>Department of Epidemiology and Biostatistics, EHESP School for Public Health, EA 4057 University Paris Descartes</institution>
,<addr-line>Paris</addr-line>
,<country>France</country>
</aff>
<aff id="aff10"><sup>10</sup>
<institution>Service Universitaire de Psychiatrie de l’Enfant et de l’Adolescent Hospitalier Le Vinatier</institution>
,<addr-line>Bron</addr-line>
,<country>France</country>
</aff>
<author-notes><fn fn-type="edited-by"><p>Edited by: Bruno Etain, Assistance Publique des Hôpitaux de Paris et INSERM, France</p>
</fn>
<fn fn-type="edited-by"><p>Reviewed by: Bernhard J. Mitterauer, Volitronics-Institute for Basic Research Psychopathology and Brain Philosophy, Austria; Pauline Jeanne Chaste, University of Pittsburgh, USA</p>
</fn>
<corresp content-type="corresp" id="cor1">*Correspondence: Sylvie Tordjman, Professor in Child Psychiatry, Chef de Pôle Hospitalo-Universitaire de Psychiatrie de l’Enfant et de l’Adolescent, 154 rue de Châtillon, 35 200 Rennes, France e-mail: <email>s.tordjman@yahoo.fr</email>
</corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Schizophrenia, a section of the journal Frontiers in Psychiatry.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>04</day>
<month>8</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="collection"><year>2014</year>
</pub-date>
<volume>5</volume>
<elocation-id>53</elocation-id>
<history><date date-type="received"><day>16</day>
<month>8</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>02</day>
<month>5</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014 Tordjman, Somogyi, Coulon, Kermarrec, Cohen, Bronsard, Bonnot, Weismann-Arcache, Botbol, Lauth, Ginchat, Roubertoux, Barburoth, Kovess, Geoffray and Xavier.</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract><p>Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal, and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene × environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of <italic>in utero</italic>
exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention, and early therapeutic intervention of ASD.</p>
</abstract>
<kwd-group><kwd>autistic spectrum disorders</kwd>
<kwd>environment</kwd>
<kwd>gene × environment interactions</kwd>
<kwd>epigenetics</kwd>
<kwd>multifactorial</kwd>
<kwd>multidisciplinary</kwd>
</kwd-group>
<counts><fig-count count="0"></fig-count>
<table-count count="3"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="217"></ref-count>
<page-count count="17"></page-count>
<word-count count="15852"></word-count>
</counts>
</article-meta>
</front>
</pmc>
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