Serveur d'exploration sur Pittsburgh

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Individual common variants exert weak effects on the risk for autism spectrum disorders.

Identifieur interne : 007B41 ( Main/Merge ); précédent : 007B40; suivant : 007B42

Individual common variants exert weak effects on the risk for autism spectrum disorders.

Auteurs : Richard Anney [Norvège] ; Lambertus Klei [États-Unis] ; Dalila Pinto [Canada] ; Joana Almeida [Portugal] ; Elena Bacchelli [Italie] ; Gillian Baird [Royaume-Uni] ; Nadia Bolshakova [Norvège] ; Sven Bölte [Allemagne] ; Patrick Bolton [Royaume-Uni] ; Thomas Bourgeron [France] ; Sean Brennan [Norvège] ; Jessica Brian [Canada] ; Jillian Casey [Irlande (pays)] ; Judith Conroy [Irlande (pays)] ; Catarina Correia [Portugal] ; Christina Corsello [États-Unis] ; Emily Crawford [États-Unis] ; Maretha De Jonge [Pays-Bas] ; Richard Delorme [France] ; Eftichia Duketis [Allemagne] ; Frederico Duque [Portugal] ; Annette Estes [États-Unis] ; Penny Farrar [Royaume-Uni] ; Bridget Fernandez [Canada] ; Susan Folstein [États-Unis] ; Eric Fombonne [Canada] ; John Gilbert [États-Unis] ; Christopher Gillberg [Suède] ; Joseph Glessner [États-Unis] ; Andrew Green [Irlande (pays)] ; Jonathan Green [Royaume-Uni] ; Stephen Guter [États-Unis] ; Elizabeth Heron [Norvège] ; Richard Holt [Royaume-Uni] ; Jennifer Howe [Canada] ; Gillian Hughes [Norvège] ; Vanessa Hus [États-Unis] ; Roberta Igliozzi [États-Unis] ; Suma Jacob [États-Unis] ; Graham Kenny [Norvège] ; Cecilia Kim [États-Unis] ; Alexander Kolevzon [États-Unis] ; Vlad Kustanovich [États-Unis] ; Clara Lajonchere [États-Unis] ; Janine Lamb [Royaume-Uni] ; Miriam Law-Smith [Norvège] ; Marion Leboyer [France] ; Ann Le Couteur [Royaume-Uni] ; Bennett Leventhal [États-Unis] ; Xiao-Qing Liu [Canada] ; Frances Lombard [Norvège] ; Catherine Lord [États-Unis] ; Linda Lotspeich [États-Unis] ; Sabata Lund [États-Unis] ; Tiago Magalhaes [Portugal] ; Carine Mantoulan [France] ; Christopher Mcdougle [États-Unis] ; Nadine Melhem [États-Unis] ; Alison Merikangas [Norvège] ; Nancy Minshew [États-Unis] ; Ghazala Mirza [Royaume-Uni] ; Jeff Munson [États-Unis] ; Carolyn Noakes [Canada] ; Gudrun Nygren [Suède] ; Katerina Papanikolaou [Grèce] ; Alistair Pagnamenta [Royaume-Uni] ; Barbara Parrini [États-Unis] ; Tara Paton [Canada] ; Andrew Pickles [Royaume-Uni] ; David Posey [États-Unis] ; Fritz Poustka [Allemagne] ; Jiannis Ragoussis [Royaume-Uni] ; Regina Regan [Irlande (pays)] ; Wendy Roberts [Canada] ; Kathryn Roeder [États-Unis] ; Bernadette Roge [France] ; Michael Rutter [Royaume-Uni] ; Sabine Schlitt [Allemagne] ; Naisha Shah [Irlande (pays)] ; Val Sheffield [États-Unis] ; Latha Soorya [États-Unis] ; Inês Sousa [Royaume-Uni] ; Vera Stoppioni [Italie] ; Nuala Sykes [Royaume-Uni] ; Raffaella Tancredi [États-Unis] ; Ann Thompson [Canada] ; Susanne Thomson [États-Unis] ; Ana Tryfon [États-Unis] ; John Tsiantis [Grèce] ; Herman Van Engeland [Pays-Bas] ; John Vincent [Canada] ; Fred Volkmar [États-Unis] ; Jacob Vorstman [Pays-Bas] ; Simon Wallace [Royaume-Uni] ; Kirsty Wing [Royaume-Uni] ; Kerstin Wittemeyer [Royaume-Uni] ; Shawn Wood [États-Unis] ; Danielle Zurawiecki [États-Unis] ; Lonnie Zwaigenbaum [Canada] ; Anthony Bailey [Royaume-Uni] ; Agatino Battaglia [États-Unis] ; Rita Cantor [États-Unis] ; Hilary Coon [Italie] ; Michael Cuccaro [États-Unis] ; Geraldine Dawson [États-Unis] ; Sean Ennis [Irlande (pays)] ; Christine Freitag [Allemagne] ; Daniel Geschwind [États-Unis] ; Jonathan Haines [États-Unis] ; Sabine Klauck [Allemagne] ; William Mcmahon [Italie] ; Elena Maestrini [Italie] ; Judith Miller [Italie] ; Anthony Monaco [Royaume-Uni] ; Stanley Nelson [États-Unis] ; John Nurnberger [États-Unis] ; Guiomar Oliveira [Portugal] ; Jeremy Parr [Royaume-Uni] ; Margaret Pericak-Vance [États-Unis] ; Joseph Piven [États-Unis] ; Gerard Schellenberg [États-Unis] ; Stephen Scherer [Canada] ; Astrid Vicente [Portugal] ; Thomas Wassink [États-Unis] ; Ellen Wijsman [États-Unis] ; Catalina Betancur [France] ; Joseph Buxbaum [États-Unis] ; Edwin Cook [États-Unis] ; Louise Gallagher [Norvège] ; Michael Gill [Norvège] ; Joachim Hallmayer [États-Unis] ; Andrew Paterson [Canada] ; James Sutcliffe [États-Unis] ; Peter Szatmari [Canada] ; Veronica Vieland [États-Unis] ; Hakon Hakonarson [États-Unis] ; Bernie Devlin [États-Unis]

Source :

RBID : Hal:inserm-00723650

Abstract

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

Url:
DOI: 10.1093/hmg/dds301

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Hal:inserm-00723650

Le document en format XML

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<address>
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<orgName>Centre de Référence du Syndrome de Prader-Willi</orgName>
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<address>
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<orgName>Department of Psychiatry</orgName>
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<tutelle active="#struct-321989" type="direct">
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<address>
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<orgName>Department of Psychiatry [Pittsburgh]</orgName>
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<addrLine>4200 Fifth AvenuePittsburgh, PA 15260</addrLine>
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</address>
<ref type="url">http://www.pitt.edu/</ref>
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<author>
<name sortKey="Merikangas, Alison" sort="Merikangas, Alison" uniqKey="Merikangas A" first="Alison" last="Merikangas">Alison Merikangas</name>
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<orgName>Division of Mental Health and Addiction</orgName>
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<addrLine>P. O. Box 4950 Nydalen - N-0424 Oslo</addrLine>
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<address>
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<name sortKey="Minshew, Nancy" sort="Minshew, Nancy" uniqKey="Minshew N" first="Nancy" last="Minshew">Nancy Minshew</name>
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<orgName>Department of Psychiatry [Pittsburgh]</orgName>
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<address>
<addrLine>Thomas Detre Hall of the Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213</addrLine>
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<address>
<addrLine>4200 Fifth AvenuePittsburgh, PA 15260</addrLine>
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</address>
<ref type="url">http://www.pitt.edu/</ref>
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<author>
<name sortKey="Mirza, Ghazala" sort="Mirza, Ghazala" uniqKey="Mirza G" first="Ghazala" last="Mirza">Ghazala Mirza</name>
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<orgName>Wellcome Trust Centre for Human Genetics</orgName>
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<address>
<addrLine>Roosevelt Drive - Headington, Oxford OX3 7BN</addrLine>
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<orgName>University of Oxford [Oxford]</orgName>
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<address>
<addrLine>Wellington Square, Oxford OX1 2JD</addrLine>
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</address>
<ref type="url">http://www.ox.ac.uk/</ref>
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<author>
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<orgName>Department of Psychiatry and Behavioral Sciences</orgName>
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</address>
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<orgName>University of Washington [Seattle]</orgName>
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<address>
<addrLine>Seattle, Washington 98105</addrLine>
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</address>
<ref type="url">http://www.washington.edu/</ref>
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<country>États-Unis</country>
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<author>
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<hal:affiliation type="laboratory" xml:id="struct-128885" status="INCOMING">
<orgName>Autism Research Unit</orgName>
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<address>
<addrLine>Toronto, Ontario, M5G 1X8</addrLine>
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</address>
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<org type="institution" xml:id="struct-300722" status="VALID">
<orgName>University of Toronto</orgName>
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<address>
<addrLine>27 King's College Circle, Toronto M5S 1A1</addrLine>
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</address>
<ref type="url">http://www.utoronto.ca/</ref>
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<address>
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<country>Canada</country>
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<settlement type="city">Toronto</settlement>
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<orgName type="university">Université de Toronto</orgName>
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</author>
<author>
<name sortKey="Nygren, Gudrun" sort="Nygren, Gudrun" uniqKey="Nygren G" first="Gudrun" last="Nygren">Gudrun Nygren</name>
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<hal:affiliation type="laboratory" xml:id="struct-22778" status="INCOMING">
<orgName>Department of Child and Adolescent Psychiatry</orgName>
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<address>
<addrLine>Göteborg</addrLine>
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</address>
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<tutelle active="#struct-302294" type="direct">
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<orgName>University of Gothenburg </orgName>
<orgName type="acronym">GU</orgName>
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<address>
<addrLine>Box 100, SE-405 30 Gothenburg</addrLine>
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</address>
<ref type="url">http://www.gu.se/english</ref>
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<country>Suède</country>
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<author>
<name sortKey="Papanikolaou, Katerina" sort="Papanikolaou, Katerina" uniqKey="Papanikolaou K" first="Katerina" last="Papanikolaou">Katerina Papanikolaou</name>
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<hal:affiliation type="laboratory" xml:id="struct-112872" status="INCOMING">
<orgName>University Department of Child Psychiatry</orgName>
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<address>
<addrLine>Medical School, Agia Sophia Children's Hospital, 115 27 Athens</addrLine>
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</address>
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<orgName>University of Athens</orgName>
<orgName type="acronym">UoA</orgName>
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<address>
<addrLine>Zografou Campus, GR-157 80 Zografou</addrLine>
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</address>
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<country>Grèce</country>
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<author>
<name sortKey="Pagnamenta, Alistair" sort="Pagnamenta, Alistair" uniqKey="Pagnamenta A" first="Alistair" last="Pagnamenta">Alistair Pagnamenta</name>
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<orgName>Wellcome Trust Centre for Human Genetics</orgName>
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<address>
<addrLine>Roosevelt Drive - Headington, Oxford OX3 7BN</addrLine>
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<tutelle active="#struct-302612" type="direct">
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<address>
<addrLine>Wellington Square, Oxford OX1 2JD</addrLine>
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</address>
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<hal:affiliation type="laboratory" xml:id="struct-57922" status="INCOMING">
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<address>
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<orgName>Program in Genetics and Genomic Biology</orgName>
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<address>
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<org type="institution" xml:id="struct-363679" status="INCOMING">
<orgName>University of Toronto McLaughlin Centre</orgName>
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<address>
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<orgName>Department of Medicine, Manchester</orgName>
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<address>
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<address>
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<hal:affiliation type="laboratory" xml:id="struct-128955" status="INCOMING">
<orgName>Department of Psychiatry</orgName>
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<address>
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<tutelle active="#struct-321989" type="direct">
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<address>
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<orgName>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy</orgName>
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<address>
<addrLine>Senckenberganlage 31 - 60325 Frankfurt am Main</addrLine>
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<orgName>Goethe-Universität Frankfurt am Main</orgName>
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<address>
<addrLine>Theodor-W.-Adorno-Platz 1 , 60323 Frankfurt am Main</addrLine>
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</address>
<ref type="url">http://www.goethe-university-frankfurt.de/</ref>
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<country>Allemagne</country>
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<author>
<name sortKey="Ragoussis, Jiannis" sort="Ragoussis, Jiannis" uniqKey="Ragoussis J" first="Jiannis" last="Ragoussis">Jiannis Ragoussis</name>
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<orgName>Wellcome Trust Centre for Human Genetics</orgName>
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<address>
<addrLine>Roosevelt Drive - Headington, Oxford OX3 7BN</addrLine>
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<tutelle active="#struct-302612" type="direct">
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<address>
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<country>Royaume-Uni</country>
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<orgName type="acronym">UCD</orgName>
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<address>
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</address>
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<orgName>Autism Research Unit</orgName>
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<address>
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<org type="institution" xml:id="struct-300722" status="VALID">
<orgName>University of Toronto</orgName>
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<address>
<addrLine>27 King's College Circle, Toronto M5S 1A1</addrLine>
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<address>
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</address>
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<address>
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<orgName>Vanderbilt University of Nashville</orgName>
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<orgName>Centers for Human Genetics Research and Molecular Neuroscience</orgName>
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<country>États-Unis</country>
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<name sortKey="Szatmari, Peter" sort="Szatmari, Peter" uniqKey="Szatmari P" first="Peter" last="Szatmari">Peter Szatmari</name>
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<orgName>Department of Psychiatry and Behavioural Neurosciences</orgName>
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<addrLine>Hamilton, Ontario, L8S 4K1</addrLine>
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<ref type="url">http://www.mcmaster.ca/</ref>
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<orgName>Battelle Center for Mathematical Medicine</orgName>
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<addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine>
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<country>États-Unis</country>
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<author>
<name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name>
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<orgName>The Center for Applied Genomics</orgName>
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<country>États-Unis</country>
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<author>
<name sortKey="Devlin, Bernie" sort="Devlin, Bernie" uniqKey="Devlin B" first="Bernie" last="Devlin">Bernie Devlin</name>
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<orgName>Department of Psychiatry [Pittsburgh]</orgName>
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<addrLine>Thomas Detre Hall of the Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213</addrLine>
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<orgName>University of Pittsburgh School of Medicine [Pittsburgh]</orgName>
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<idno type="DOI">10.1093/hmg/dds301</idno>
<series>
<title level="j">Human Molecular Genetics</title>
<idno type="ISSN">0964-6906</idno>
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<date type="datePub">2012-11-01</date>
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<front>
<div type="abstract" xml:lang="en">While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.</div>
</front>
</TEI>
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