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Genetic Variation and Autism: A Field Synopsis and Systematic Meta-Analysis
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Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach

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Theoreo srl spin off company of the University of Salerno, Via degli Ulivi, 3, 84090 Montecorvino Pugliano (SA), Italy
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Faculty of Social Sciences, Health Sciences Unit, Tampere University, Arvo Ylpön Katu 34, 33014 Tampere, Finland
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Bio-Modeling System, 3, Rue De L’arrivee. 75015 Paris, France
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Department of science medicine translational, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy
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Promete srl, Piazzale Tecchio 45, 80125 Napoli, Italy
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Azienda Sanitaria Locale (ASL) Salerno, Via Nizza, 146, 84125 Salerno (SA), Italy
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National University of Ireland Galaway, University Road, Galaway, Ireland
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Massachusetts General Hospital, Fruit Street, 55, Boston, MA 02114, USA
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John Hopkins School of Public Health and the Wendy Klag Center for Autism and Developmental Disabilities, 615 N. Wolfe St, Baltimore, MD 21205, USA
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Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Inserm UMR 1239, Rouen University of Normandy, 25 rue Tesnière, 76130 Mont-Saint-Aignan, France
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Medinok Spa, Via Palazziello, 80040 Volla (NA), Italy
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Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The Netherlands
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Danone Nutricia Research, Uppsalalaan, 12, 3584 CT Utrecht, The Netherlands
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Institut National de Recherche Pour L’agriculture, L’alimentation et L’environnement (INRAE), AgroParisTech, Micalis Institute, Université Paris-Saclay, 78350 Jouy-en-Josas, France
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Consiglio Nazionale delle Ricerche (CNR), Piazzale Aldo Moro, 7, 00185 Roma, Italy
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Euformatics, Tekniikantie, 02150 Espoo, Finland
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European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 3, 84125 Salerno (SA), Italy
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Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(10), 743; https://doi.org/10.3390/brainsci10100743
Received: 29 August 2020 / Revised: 7 October 2020 / Accepted: 14 October 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Advances in Autism Research)
Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response. View Full-Text
Keywords: microbiome; metabolomics; autism; study design; biomarker discovery; precise medicine microbiome; metabolomics; autism; study design; biomarker discovery; precise medicine
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Troisi, J.; Autio, R.; Beopoulos, T.; Bravaccio, C.; Carraturo, F.; Corrivetti, G.; Cunningham, S.; Devane, S.; Fallin, D.; Fetissov, S.; Gea, M.; Giorgi, A.; Iris, F.; Joshi, L.; Kadzielski, S.; Kraneveld, A.; Kumar, H.; Ladd-Acosta, C.; Leader, G.; Mannion, A.; Maximin, E.; Mezzelani, A.; Milanesi, L.; Naudon, L.; Peralta Marzal, L.N.; Perez Pardo, P.; Prince, N.Z.; Rabot, S.; Roeselers, G.; Roos, C.; Roussin, L.; Scala, G.; Tuccinardi, F.P.; Fasano, A. Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach. Brain Sci. 2020, 10, 743.

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