Lack of replication of previous autism spectrum disorder GWAS hits in European populations.
Identifieur interne : 000908 ( Main/Exploration ); précédent : 000907; suivant : 000909Lack of replication of previous autism spectrum disorder GWAS hits in European populations.
Auteurs : Bàrbara Torrico [Espagne] ; Andreas G. Chiocchetti [Allemagne] ; Elena Bacchelli [Italie] ; Elisabetta Trabetti [Italie] ; Amaia Hervás [Espagne] ; Barbara Franke [Pays-Bas] ; Jan K. Buitelaar [Pays-Bas] ; Nanda Rommelse [Pays-Bas] ; Afsheen Yousaf [Allemagne] ; Eftichia Duketis [Allemagne] ; Christine M. Freitag [Allemagne] ; Rafaela Caballero-Andaluz [Espagne] ; Amalia Martinez-Mir [Espagne] ; Francisco G. Scholl [Espagne] ; Marta Ribasés [Espagne] ; Agatino Battaglia [Italie] ; Giovanni Malerba [Italie] ; Richard Delorme [France] ; Marion Benabou [France] ; Elena Maestrini [Italie] ; Thomas Bourgeron [France] ; Bru Cormand [Espagne] ; Claudio Toma [Espagne]Source :
- Autism research : official journal of the International Society for Autism Research [ 1939-3806 ] ; 2017.
Abstract
Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI = 0.84-1.32) for rs10513025, 1.0002 (95% CI = 0.93-1.08) for rs4141463 and 1.01 (95% CI = 0.92-1.1) for rs4307059, with no significant P-values (rs10513025, P = 0.73; rs4141463, P = 0.95; rs4307059, P = 0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. Autism Res 2017, 10: 202-211. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
DOI: 10.1002/aur.1662
PubMed: 27417655
Affiliations:
- Allemagne, Espagne, France, Italie, Pays-Bas
- Catalogne, District de Darmstadt, Hesse (Land), Toscane, Île-de-France
- Barcelone, Francfort-sur-le-Main, Paris, Pise
- Université autonome de Barcelone, Université de Barcelone
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Freitag</name><affiliation wicri:level="3"><nlm:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Caballero Andaluz, Rafaela" sort="Caballero Andaluz, Rafaela" uniqKey="Caballero Andaluz R" first="Rafaela" last="Caballero-Andaluz">Rafaela Caballero-Andaluz</name><affiliation wicri:level="1"><nlm:affiliation>Autism unit, department of Psychiatry, University of Seville, C/ San Fernando 4, 41004, Sevilla, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Autism unit, department of Psychiatry, University of Seville, C/ San Fernando 4, 41004, Sevilla</wicri:regionArea><wicri:noRegion>Sevilla</wicri:noRegion></affiliation></author><author><name sortKey="Martinez Mir, Amalia" sort="Martinez Mir, Amalia" uniqKey="Martinez Mir A" first="Amalia" last="Martinez-Mir">Amalia Martinez-Mir</name><affiliation wicri:level="1"><nlm:affiliation>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation></author><author><name sortKey="Scholl, Francisco G" sort="Scholl, Francisco G" uniqKey="Scholl F" first="Francisco G" last="Scholl">Francisco G. Scholl</name><affiliation wicri:level="1"><nlm:affiliation>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation></author><author><name sortKey="Ribases, Marta" sort="Ribases, Marta" uniqKey="Ribases M" first="Marta" last="Ribasés">Marta Ribasés</name><affiliation wicri:level="4"><nlm:affiliation>Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Battaglia, Agatino" sort="Battaglia, Agatino" uniqKey="Battaglia A" first="Agatino" last="Battaglia">Agatino Battaglia</name><affiliation wicri:level="3"><nlm:affiliation>Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, via dei Giacinti 2, 56128 Calambrone, Pisa, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, via dei Giacinti 2, 56128 Calambrone, Pisa</wicri:regionArea><placeName><settlement type="city">Pise</settlement><region nuts="2">Toscane</region></placeName></affiliation></author><author><name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134, Verona</wicri:regionArea><wicri:noRegion>Verona</wicri:noRegion></affiliation></author><author><name sortKey="Delorme, Richard" sort="Delorme, Richard" uniqKey="Delorme R" first="Richard" last="Delorme">Richard Delorme</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Benabou, Marion" sort="Benabou, Marion" uniqKey="Benabou M" first="Marion" last="Benabou">Marion Benabou</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Maestrini, Elena" sort="Maestrini, Elena" uniqKey="Maestrini E" first="Elena" last="Maestrini">Elena Maestrini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacy and Biotechnology, University of Bologna, via Selmi 3, 40126, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Pharmacy and Biotechnology, University of Bologna, via Selmi 3, 40126, Bologna</wicri:regionArea><wicri:noRegion>Bologna</wicri:noRegion></affiliation></author><author><name sortKey="Bourgeron, Thomas" sort="Bourgeron, Thomas" uniqKey="Bourgeron T" first="Thomas" last="Bourgeron">Thomas Bourgeron</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Cormand, Bru" sort="Cormand, Bru" uniqKey="Cormand B" first="Bru" last="Cormand">Bru Cormand</name><affiliation wicri:level="4"><nlm:affiliation>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université de Barcelone</orgName></affiliation></author><author><name sortKey="Toma, Claudio" sort="Toma, Claudio" uniqKey="Toma C" first="Claudio" last="Toma">Claudio Toma</name><affiliation wicri:level="4"><nlm:affiliation>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. 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Diagonal 643, 08028, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université de Barcelone</orgName></affiliation></author><author><name sortKey="Chiocchetti, Andreas G" sort="Chiocchetti, Andreas G" uniqKey="Chiocchetti A" first="Andreas G" last="Chiocchetti">Andreas G. Chiocchetti</name><affiliation wicri:level="3"><nlm:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Bacchelli, Elena" sort="Bacchelli, Elena" uniqKey="Bacchelli E" first="Elena" last="Bacchelli">Elena Bacchelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacy and Biotechnology, University of Bologna, via Selmi 3, 40126, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Pharmacy and Biotechnology, University of Bologna, via Selmi 3, 40126, Bologna</wicri:regionArea><wicri:noRegion>Bologna</wicri:noRegion></affiliation></author><author><name sortKey="Trabetti, Elisabetta" sort="Trabetti, Elisabetta" uniqKey="Trabetti E" first="Elisabetta" last="Trabetti">Elisabetta Trabetti</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134, Verona</wicri:regionArea><wicri:noRegion>Verona</wicri:noRegion></affiliation></author><author><name sortKey="Hervas, Amaia" sort="Hervas, Amaia" uniqKey="Hervas A" first="Amaia" last="Hervás">Amaia Hervás</name><affiliation wicri:level="3"><nlm:affiliation>Child and Adolescent Mental Health Unit, University Hospital MutuaTerrassa, Plaza del Dr Robert s/n, 08221, Terrassa, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Child and Adolescent Mental Health Unit, University Hospital MutuaTerrassa, Plaza del Dr Robert s/n, 08221, Terrassa, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Franke, Barbara" sort="Franke, Barbara" uniqKey="Franke B" first="Barbara" last="Franke">Barbara Franke</name><affiliation wicri:level="1"><nlm:affiliation>Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Geert Grooteplein-Zuid 10, 6525, GA Nijmegen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics, Geert Grooteplein-Zuid 10, 6525, GA Nijmegen</wicri:regionArea><wicri:noRegion>GA Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Buitelaar, Jan K" sort="Buitelaar, Jan K" uniqKey="Buitelaar J" first="Jan K" last="Buitelaar">Jan K. Buitelaar</name><affiliation wicri:level="1"><nlm:affiliation>Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Geert Grooteplein Noord 21, 6525, EZ Nijmegen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Geert Grooteplein Noord 21, 6525, EZ Nijmegen</wicri:regionArea><wicri:noRegion>EZ Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Rommelse, Nanda" sort="Rommelse, Nanda" uniqKey="Rommelse N" first="Nanda" last="Rommelse">Nanda Rommelse</name><affiliation wicri:level="1"><nlm:affiliation>Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Geert Grooteplein-Zuid 10, 6525, GA Nijmegen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Geert Grooteplein-Zuid 10, 6525, GA Nijmegen</wicri:regionArea><wicri:noRegion>GA Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Yousaf, Afsheen" sort="Yousaf, Afsheen" uniqKey="Yousaf A" first="Afsheen" last="Yousaf">Afsheen Yousaf</name><affiliation wicri:level="3"><nlm:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Duketis, Eftichia" sort="Duketis, Eftichia" uniqKey="Duketis E" first="Eftichia" last="Duketis">Eftichia Duketis</name><affiliation wicri:level="3"><nlm:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Freitag, Christine M" sort="Freitag, Christine M" uniqKey="Freitag C" first="Christine M" last="Freitag">Christine M. Freitag</name><affiliation wicri:level="3"><nlm:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, JW Goethe University, Deutschordenstraße 50 60528 Frankfurt am Main, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Caballero Andaluz, Rafaela" sort="Caballero Andaluz, Rafaela" uniqKey="Caballero Andaluz R" first="Rafaela" last="Caballero-Andaluz">Rafaela Caballero-Andaluz</name><affiliation wicri:level="1"><nlm:affiliation>Autism unit, department of Psychiatry, University of Seville, C/ San Fernando 4, 41004, Sevilla, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Autism unit, department of Psychiatry, University of Seville, C/ San Fernando 4, 41004, Sevilla</wicri:regionArea><wicri:noRegion>Sevilla</wicri:noRegion></affiliation></author><author><name sortKey="Martinez Mir, Amalia" sort="Martinez Mir, Amalia" uniqKey="Martinez Mir A" first="Amalia" last="Martinez-Mir">Amalia Martinez-Mir</name><affiliation wicri:level="1"><nlm:affiliation>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation></author><author><name sortKey="Scholl, Francisco G" sort="Scholl, Francisco G" uniqKey="Scholl F" first="Francisco G" last="Scholl">Francisco G. Scholl</name><affiliation wicri:level="1"><nlm:affiliation>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot s/n, 41013, Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation></author><author><name sortKey="Ribases, Marta" sort="Ribases, Marta" uniqKey="Ribases M" first="Marta" last="Ribasés">Marta Ribasés</name><affiliation wicri:level="4"><nlm:affiliation>Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Battaglia, Agatino" sort="Battaglia, Agatino" uniqKey="Battaglia A" first="Agatino" last="Battaglia">Agatino Battaglia</name><affiliation wicri:level="3"><nlm:affiliation>Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, via dei Giacinti 2, 56128 Calambrone, Pisa, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, via dei Giacinti 2, 56128 Calambrone, Pisa</wicri:regionArea><placeName><settlement type="city">Pise</settlement><region nuts="2">Toscane</region></placeName></affiliation></author><author><name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Strada le Grazie 8, 37134, Verona</wicri:regionArea><wicri:noRegion>Verona</wicri:noRegion></affiliation></author><author><name sortKey="Delorme, Richard" sort="Delorme, Richard" uniqKey="Delorme R" first="Richard" last="Delorme">Richard Delorme</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Benabou, Marion" sort="Benabou, Marion" uniqKey="Benabou M" first="Marion" last="Benabou">Marion Benabou</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Maestrini, Elena" sort="Maestrini, Elena" uniqKey="Maestrini E" first="Elena" last="Maestrini">Elena Maestrini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacy and Biotechnology, University of Bologna, via Selmi 3, 40126, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Pharmacy and Biotechnology, University of Bologna, via Selmi 3, 40126, Bologna</wicri:regionArea><wicri:noRegion>Bologna</wicri:noRegion></affiliation></author><author><name sortKey="Bourgeron, Thomas" sort="Bourgeron, Thomas" uniqKey="Bourgeron T" first="Thomas" last="Bourgeron">Thomas Bourgeron</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25, rue du docteur Roux, 75015, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Cormand, Bru" sort="Cormand, Bru" uniqKey="Cormand B" first="Bru" last="Cormand">Bru Cormand</name><affiliation wicri:level="4"><nlm:affiliation>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université de Barcelone</orgName></affiliation></author><author><name sortKey="Toma, Claudio" sort="Toma, Claudio" uniqKey="Toma C" first="Claudio" last="Toma">Claudio Toma</name><affiliation wicri:level="4"><nlm:affiliation>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region><settlement type="city">Barcelone</settlement></placeName><orgName type="university">Université de Barcelone</orgName></affiliation></author></analytic><series><title level="j">Autism research : official journal of the International Society for Autism Research</title><idno type="eISSN">1939-3806</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI = 0.84-1.32) for rs10513025, 1.0002 (95% CI = 0.93-1.08) for rs4141463 and 1.01 (95% CI = 0.92-1.1) for rs4307059, with no significant P-values (rs10513025, P = 0.73; rs4141463, P = 0.95; rs4307059, P = 0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. Autism Res 2017, 10: 202-211. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Espagne</li><li>France</li><li>Italie</li><li>Pays-Bas</li></country><region><li>Catalogne</li><li>District de Darmstadt</li><li>Hesse (Land)</li><li>Toscane</li><li>Île-de-France</li></region><settlement><li>Barcelone</li><li>Francfort-sur-le-Main</li><li>Paris</li><li>Pise</li></settlement><orgName><li>Université autonome de Barcelone</li><li>Université de Barcelone</li></orgName></list><tree><country name="Espagne"><region name="Catalogne"><name sortKey="Torrico, Barbara" sort="Torrico, Barbara" uniqKey="Torrico B" first="Bàrbara" last="Torrico">Bàrbara Torrico</name></region><name sortKey="Caballero Andaluz, Rafaela" sort="Caballero Andaluz, Rafaela" uniqKey="Caballero Andaluz R" first="Rafaela" last="Caballero-Andaluz">Rafaela Caballero-Andaluz</name><name sortKey="Cormand, Bru" sort="Cormand, Bru" uniqKey="Cormand B" first="Bru" last="Cormand">Bru Cormand</name><name sortKey="Hervas, Amaia" sort="Hervas, Amaia" uniqKey="Hervas A" first="Amaia" last="Hervás">Amaia Hervás</name><name sortKey="Martinez Mir, Amalia" sort="Martinez Mir, Amalia" uniqKey="Martinez Mir A" first="Amalia" last="Martinez-Mir">Amalia Martinez-Mir</name><name sortKey="Ribases, Marta" sort="Ribases, Marta" uniqKey="Ribases M" first="Marta" last="Ribasés">Marta Ribasés</name><name sortKey="Scholl, Francisco G" sort="Scholl, Francisco G" uniqKey="Scholl F" first="Francisco G" last="Scholl">Francisco G. Scholl</name><name sortKey="Toma, Claudio" sort="Toma, Claudio" uniqKey="Toma C" first="Claudio" last="Toma">Claudio Toma</name></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Chiocchetti, Andreas G" sort="Chiocchetti, Andreas G" uniqKey="Chiocchetti A" first="Andreas G" last="Chiocchetti">Andreas G. Chiocchetti</name></region><name sortKey="Duketis, Eftichia" sort="Duketis, Eftichia" uniqKey="Duketis E" first="Eftichia" last="Duketis">Eftichia Duketis</name><name sortKey="Freitag, Christine M" sort="Freitag, Christine M" uniqKey="Freitag C" first="Christine M" last="Freitag">Christine M. Freitag</name><name sortKey="Yousaf, Afsheen" sort="Yousaf, Afsheen" uniqKey="Yousaf A" first="Afsheen" last="Yousaf">Afsheen Yousaf</name></country><country name="Italie"><noRegion><name sortKey="Bacchelli, Elena" sort="Bacchelli, Elena" uniqKey="Bacchelli E" first="Elena" last="Bacchelli">Elena Bacchelli</name></noRegion><name sortKey="Battaglia, Agatino" sort="Battaglia, Agatino" uniqKey="Battaglia A" first="Agatino" last="Battaglia">Agatino Battaglia</name><name sortKey="Maestrini, Elena" sort="Maestrini, Elena" uniqKey="Maestrini E" first="Elena" last="Maestrini">Elena Maestrini</name><name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name><name sortKey="Trabetti, Elisabetta" sort="Trabetti, Elisabetta" uniqKey="Trabetti E" first="Elisabetta" last="Trabetti">Elisabetta Trabetti</name></country><country name="Pays-Bas"><noRegion><name sortKey="Franke, Barbara" sort="Franke, Barbara" uniqKey="Franke B" first="Barbara" last="Franke">Barbara Franke</name></noRegion><name sortKey="Buitelaar, Jan K" sort="Buitelaar, Jan K" uniqKey="Buitelaar J" first="Jan K" last="Buitelaar">Jan K. Buitelaar</name><name sortKey="Rommelse, Nanda" sort="Rommelse, Nanda" uniqKey="Rommelse N" first="Nanda" last="Rommelse">Nanda Rommelse</name></country><country name="France"><region name="Île-de-France"><name sortKey="Delorme, Richard" sort="Delorme, Richard" uniqKey="Delorme R" first="Richard" last="Delorme">Richard Delorme</name></region><name sortKey="Benabou, Marion" sort="Benabou, Marion" uniqKey="Benabou M" first="Marion" last="Benabou">Marion Benabou</name><name sortKey="Bourgeron, Thomas" sort="Bourgeron, Thomas" uniqKey="Bourgeron T" first="Thomas" last="Bourgeron">Thomas Bourgeron</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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