Gene X environment interactions in autism spectrum disorders: role of epigenetic mechanisms

Sylvie Tordjman, Eszter Somogyi, Nathalie Coulon, Solenn Kermarrec, David Cohen, Guillaume Bronsard, Olivier Bonnot, Catherine Weismann-Arcache, Michel Botbol, Bertrand Lauth, Vincent Ginchat, Pierre Roubertoux, Marianne Barburoth, Viviane Kovess, Marie-Maude Geoffray, Jean Xavier

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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 in utero 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.
Original languageEnglish
Article number53
Number of pages17
JournalFrontiers in Psychiatry
Volume5
DOIs
Publication statusPublished - 4 Aug 2014

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