Individual common variants exert weak effects on the risk for autism spectrum disorders.
Identifieur interne : 000344 ( Hal/Corpus ); précédent : 000343; suivant : 000345Individual common variants exert weak effects on the risk for autism spectrum disorders.
Auteurs : Richard Anney ; Lambertus Klei ; Dalila Pinto ; Joana Almeida ; Elena Bacchelli ; Gillian Baird ; Nadia Bolshakova ; Sven Bölte ; Patrick Bolton ; Thomas Bourgeron ; Sean Brennan ; Jessica Brian ; Jillian Casey ; Judith Conroy ; Catarina Correia ; Christina Corsello ; Emily Crawford ; Maretha De Jonge ; Richard Delorme ; Eftichia Duketis ; Frederico Duque ; Annette Estes ; Penny Farrar ; Bridget Fernandez ; Susan Folstein ; Eric Fombonne ; John Gilbert ; Christopher Gillberg ; Joseph Glessner ; Andrew Green ; Jonathan Green ; Stephen Guter ; Elizabeth Heron ; Richard Holt ; Jennifer Howe ; Gillian Hughes ; Vanessa Hus ; Roberta Igliozzi ; Suma Jacob ; Graham Kenny ; Cecilia Kim ; Alexander Kolevzon ; Vlad Kustanovich ; Clara Lajonchere ; Janine Lamb ; Miriam Law-Smith ; Marion Leboyer ; Ann Le Couteur ; Bennett Leventhal ; Xiao-Qing Liu ; Frances Lombard ; Catherine Lord ; Linda Lotspeich ; Sabata Lund ; Tiago Magalhaes ; Carine Mantoulan ; Christopher Mcdougle ; Nadine Melhem ; Alison Merikangas ; Nancy Minshew ; Ghazala Mirza ; Jeff Munson ; Carolyn Noakes ; Gudrun Nygren ; Katerina Papanikolaou ; Alistair Pagnamenta ; Barbara Parrini ; Tara Paton ; Andrew Pickles ; David Posey ; Fritz Poustka ; Jiannis Ragoussis ; Regina Regan ; Wendy Roberts ; Kathryn Roeder ; Bernadette Roge ; Michael Rutter ; Sabine Schlitt ; Naisha Shah ; Val Sheffield ; Latha Soorya ; Inês Sousa ; Vera Stoppioni ; Nuala Sykes ; Raffaella Tancredi ; Ann Thompson ; Susanne Thomson ; Ana Tryfon ; John Tsiantis ; Herman Van Engeland ; John Vincent ; Fred Volkmar ; Jacob Vorstman ; Simon Wallace ; Kirsty Wing ; Kerstin Wittemeyer ; Shawn Wood ; Danielle Zurawiecki ; Lonnie Zwaigenbaum ; Anthony Bailey ; Agatino Battaglia ; Rita Cantor ; Hilary Coon ; Michael Cuccaro ; Geraldine Dawson ; Sean Ennis ; Christine Freitag ; Daniel Geschwind ; Jonathan Haines ; Sabine Klauck ; William Mcmahon ; Elena Maestrini ; Judith Miller ; Anthony Monaco ; Stanley Nelson ; John Nurnberger ; Guiomar Oliveira ; Jeremy Parr ; Margaret Pericak-Vance ; Joseph Piven ; Gerard Schellenberg ; Stephen Scherer ; Astrid Vicente ; Thomas Wassink ; Ellen Wijsman ; Catalina Betancur ; Joseph Buxbaum ; Edwin Cook ; Louise Gallagher ; Michael Gill ; Joachim Hallmayer ; Andrew Paterson ; James Sutcliffe ; Peter Szatmari ; Veronica Vieland ; Hakon Hakonarson ; Bernie DevlinSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2012-11-01.
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-00723650Le document en format XML
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<author><name sortKey="Zurawiecki, Danielle" sort="Zurawiecki, Danielle" uniqKey="Zurawiecki D" first="Danielle" last="Zurawiecki">Danielle Zurawiecki</name>
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<author><name sortKey="Zwaigenbaum, Lonnie" sort="Zwaigenbaum, Lonnie" uniqKey="Zwaigenbaum L" first="Lonnie" last="Zwaigenbaum">Lonnie Zwaigenbaum</name>
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<author><name sortKey="Gill, Michael" sort="Gill, Michael" uniqKey="Gill M" first="Michael" last="Gill">Michael Gill</name>
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<author><name sortKey="Hallmayer, Joachim" sort="Hallmayer, Joachim" uniqKey="Hallmayer J" first="Joachim" last="Hallmayer">Joachim Hallmayer</name>
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<author><name sortKey="Paterson, Andrew" sort="Paterson, Andrew" uniqKey="Paterson A" first="Andrew" last="Paterson">Andrew Paterson</name>
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<desc> <address> <addrLine>Centre for Applied Genomics - Toronto, Ontario, M5G 1L7</addrLine>
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<tutelle active="#struct-363679" type="direct"><org type="institution" xml:id="struct-363679" status="INCOMING"> <orgName>University of Toronto McLaughlin Centre</orgName>
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<author><name sortKey="Sutcliffe, James" sort="Sutcliffe, James" uniqKey="Sutcliffe J" first="James" last="Sutcliffe">James Sutcliffe</name>
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<desc> <address> <addrLine>Nashville, Tennessee 37232</addrLine>
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<tutelle active="#struct-331242" type="direct"><org type="institution" xml:id="struct-331242" status="INCOMING"> <orgName>Centers for Human Genetics Research and Molecular Neuroscience</orgName>
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<author><name sortKey="Szatmari, Peter" sort="Szatmari, Peter" uniqKey="Szatmari P" first="Peter" last="Szatmari">Peter Szatmari</name>
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<desc> <address> <addrLine>Hamilton, Ontario, L8S 4K1</addrLine>
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</address>
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</address>
<ref type="url">http://www.mcmaster.ca/</ref>
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<tutelle active="#struct-361531" type="direct"><org type="institution" xml:id="struct-361531" status="INCOMING"> <orgName>Offord Centre for Child Studies</orgName>
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<author><name sortKey="Vieland, Veronica" sort="Vieland, Veronica" uniqKey="Vieland V" first="Veronica" last="Vieland">Veronica Vieland</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-150256" status="INCOMING"> <orgName>Battelle Center for Mathematical Medicine</orgName>
<desc> <address> <addrLine>700 Childrens Dr, Columbus, OH 43205</addrLine>
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<desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine>
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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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<desc> <address> <addrLine>Philadelphia, PA 19104</addrLine>
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<author><name sortKey="Devlin, Bernie" sort="Devlin, Bernie" uniqKey="Devlin B" first="Bernie" last="Devlin">Bernie Devlin</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-128859" status="VALID"> <orgName>Department of Psychiatry [Pittsburgh]</orgName>
<desc> <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>
<ref type="url">http://www.wpic.pitt.edu/</ref>
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</address>
<ref type="url">http://www.pitt.edu/</ref>
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</analytic>
<idno type="DOI">10.1093/hmg/dds301</idno>
<series><title level="j">Human Molecular Genetics</title>
<idno type="ISSN">0964-6906</idno>
<imprint><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>
<hal api="V3"> <titleStmt> <title xml:lang="en">Individual common variants exert weak effects on the risk for autism spectrum disorders.</title>
<author role="aut"> <persName> <forename type="first">Richard</forename>
<surname>Anney</surname>
</persName>
<idno type="halauthorid">529413</idno>
<affiliation ref="#struct-128860"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Lambertus</forename>
<surname>Klei</surname>
</persName>
<idno type="halauthorid">529412</idno>
<affiliation ref="#struct-128859"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Dalila</forename>
<surname>Pinto</surname>
</persName>
<idno type="halauthorid">529410</idno>
<affiliation ref="#struct-150249"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Joana</forename>
<surname>Almeida</surname>
</persName>
<idno type="halauthorid">529419</idno>
<affiliation ref="#struct-128866"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Elena</forename>
<surname>Bacchelli</surname>
</persName>
<idno type="halauthorid">304087</idno>
<affiliation ref="#struct-57919"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Gillian</forename>
<surname>Baird</surname>
</persName>
<idno type="halauthorid">529421</idno>
<affiliation ref="#struct-128882"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Nadia</forename>
<surname>Bolshakova</surname>
</persName>
<idno type="halauthorid">529423</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Sven</forename>
<surname>Bölte</surname>
</persName>
<idno type="halauthorid">483802</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Patrick</forename>
<forename type="middle">F.</forename>
<surname>Bolton</surname>
</persName>
<idno type="halauthorid">529424</idno>
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<author role="aut"> <persName> <forename type="first">Thomas</forename>
<surname>Bourgeron</surname>
</persName>
<idno type="halauthorid">157767</idno>
<affiliation ref="#struct-175056"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Sean</forename>
<surname>Brennan</surname>
</persName>
<idno type="halauthorid">172306</idno>
<affiliation ref="#struct-128860"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Jessica</forename>
<surname>Brian</surname>
</persName>
<idno type="halauthorid">529425</idno>
<affiliation ref="#struct-128885"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Jillian</forename>
<surname>Casey</surname>
</persName>
<idno type="halauthorid">529429</idno>
<affiliation ref="#struct-128862"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Judith</forename>
<surname>Conroy</surname>
</persName>
<idno type="halauthorid">529415</idno>
<affiliation ref="#struct-128862"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Catarina</forename>
<surname>Correia</surname>
</persName>
<idno type="halauthorid">529417</idno>
<affiliation ref="#struct-128863"></affiliation>
<affiliation ref="#struct-128864"></affiliation>
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<author role="aut"> <persName> <forename type="first">Christina</forename>
<surname>Corsello</surname>
</persName>
<idno type="halauthorid">529432</idno>
<affiliation ref="#struct-128932"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Emily</forename>
<forename type="middle">L.</forename>
<surname>Crawford</surname>
</persName>
<idno type="halauthorid">529433</idno>
<affiliation ref="#struct-128933"></affiliation>
<affiliation ref="#struct-128988"></affiliation>
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<author role="aut"> <persName> <forename type="first">Maretha</forename>
<surname>De Jonge</surname>
</persName>
<idno type="halauthorid">529437</idno>
<affiliation ref="#struct-128605"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Richard</forename>
<surname>Delorme</surname>
</persName>
<idno type="halauthorid">117622</idno>
<affiliation ref="#struct-5439"></affiliation>
<affiliation ref="#struct-266797"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Eftichia</forename>
<surname>Duketis</surname>
</persName>
<idno type="halauthorid">483799</idno>
<affiliation ref="#struct-112863"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Frederico</forename>
<surname>Duque</surname>
</persName>
<idno type="halauthorid">529439</idno>
<affiliation ref="#struct-128866"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Annette</forename>
<surname>Estes</surname>
</persName>
<idno type="halauthorid">529440</idno>
<affiliation ref="#struct-128937"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Penny</forename>
<surname>Farrar</surname>
</persName>
<idno type="halauthorid">529441</idno>
<affiliation ref="#struct-128858"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Bridget</forename>
<forename type="middle">A.</forename>
<surname>Fernandez</surname>
</persName>
<idno type="halauthorid">529442</idno>
<affiliation ref="#struct-128941"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Susan</forename>
<forename type="middle">E.</forename>
<surname>Folstein</surname>
</persName>
<idno type="halauthorid">529443</idno>
<affiliation ref="#struct-200667"></affiliation>
<affiliation ref="#struct-128942"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Eric</forename>
<surname>Fombonne</surname>
</persName>
<idno type="halauthorid">264437</idno>
<affiliation ref="#struct-199223"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">John</forename>
<surname>Gilbert</surname>
</persName>
<idno type="halauthorid">529445</idno>
<affiliation ref="#struct-128942"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Christopher</forename>
<surname>Gillberg</surname>
</persName>
<idno type="halauthorid">140686</idno>
<affiliation ref="#struct-22778"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Joseph</forename>
<forename type="middle">T.</forename>
<surname>Glessner</surname>
</persName>
<idno type="halauthorid">528992</idno>
<affiliation ref="#struct-128717"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Andrew</forename>
<surname>Green</surname>
</persName>
<idno type="halauthorid">518196</idno>
<affiliation ref="#struct-128862"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Jonathan</forename>
<surname>Green</surname>
</persName>
<idno type="halauthorid">529447</idno>
<affiliation ref="#struct-112882"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Stephen</forename>
<forename type="middle">J.</forename>
<surname>Guter</surname>
</persName>
<idno type="halauthorid">529448</idno>
<affiliation ref="#struct-128716"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Elizabeth</forename>
<forename type="middle">A.</forename>
<surname>Heron</surname>
</persName>
<idno type="halauthorid">529449</idno>
<affiliation ref="#struct-128860"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Richard</forename>
<surname>Holt</surname>
</persName>
<idno type="halauthorid">529451</idno>
<affiliation ref="#struct-128858"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Jennifer</forename>
<forename type="middle">L.</forename>
<surname>Howe</surname>
</persName>
<idno type="halauthorid">529452</idno>
<affiliation ref="#struct-150249"></affiliation>
<affiliation ref="#struct-128857"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Gillian</forename>
<surname>Hughes</surname>
</persName>
<idno type="halauthorid">529453</idno>
<affiliation ref="#struct-128860"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Vanessa</forename>
<surname>Hus</surname>
</persName>
<idno type="halauthorid">529454</idno>
<affiliation ref="#struct-128932"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Roberta</forename>
<surname>Igliozzi</surname>
</persName>
<idno type="halauthorid">529455</idno>
<affiliation ref="#struct-57922"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Suma</forename>
<surname>Jacob</surname>
</persName>
<idno type="halauthorid">752755</idno>
<affiliation ref="#struct-128716"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Graham</forename>
<forename type="middle">P.</forename>
<surname>Kenny</surname>
</persName>
<idno type="halauthorid">752874</idno>
<affiliation ref="#struct-128860"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Cecilia</forename>
<surname>Kim</surname>
</persName>
<idno type="halauthorid">529456</idno>
<affiliation ref="#struct-128717"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Alexander</forename>
<surname>Kolevzon</surname>
</persName>
<idno type="halauthorid">529458</idno>
<affiliation ref="#struct-57911"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Vlad</forename>
<surname>Kustanovich</surname>
</persName>
<idno type="halauthorid">529460</idno>
<affiliation ref="#struct-128949"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Clara</forename>
<forename type="middle">M.</forename>
<surname>Lajonchere</surname>
</persName>
<idno type="halauthorid">529461</idno>
<affiliation ref="#struct-128949"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Janine</forename>
<forename type="middle">A.</forename>
<surname>Lamb</surname>
</persName>
<idno type="halauthorid">529462</idno>
<affiliation ref="#struct-128950"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Miriam</forename>
<surname>Law-Smith</surname>
</persName>
<idno type="halauthorid">752759</idno>
<affiliation ref="#struct-128860"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Marion</forename>
<surname>Leboyer</surname>
</persName>
<idno type="halauthorid">117627</idno>
<affiliation ref="#struct-266797"></affiliation>
<affiliation ref="#struct-30690"></affiliation>
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<author role="aut"> <persName> <forename type="first">Ann</forename>
<surname>Le Couteur</surname>
</persName>
<idno type="halauthorid">529464</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Bennett</forename>
<forename type="middle">L.</forename>
<surname>Leventhal</surname>
</persName>
<idno type="halauthorid">529465</idno>
<affiliation ref="#struct-200668"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Xiao-Qing</forename>
<surname>Liu</surname>
</persName>
<idno type="halauthorid">529467</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Frances</forename>
<surname>Lombard</surname>
</persName>
<idno type="halauthorid">752761</idno>
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<author role="aut"> <persName> <forename type="first">Nancy</forename>
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<author role="aut"> <persName> <forename type="first">Ghazala</forename>
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<author role="aut"> <persName> <forename type="first">Jeff</forename>
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<author role="aut"> <persName> <forename type="first">Carolyn</forename>
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<idno type="halauthorid">529484</idno>
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<idno type="halauthorid">140682</idno>
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<author role="aut"> <persName> <forename type="first">Katerina</forename>
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<idno type="halauthorid">529487</idno>
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<author role="aut"> <persName> <forename type="first">Alistair</forename>
<forename type="middle">T.</forename>
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<idno type="halauthorid">529411</idno>
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<author role="aut"> <persName> <forename type="first">Barbara</forename>
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<idno type="halauthorid">529489</idno>
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<author role="aut"> <persName> <forename type="first">Tara</forename>
<surname>Paton</surname>
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<idno type="halauthorid">529490</idno>
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<author role="aut"> <persName> <forename type="first">Andrew</forename>
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<author role="aut"> <persName> <forename type="first">David</forename>
<forename type="middle">J.</forename>
<surname>Posey</surname>
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<idno type="halauthorid">529494</idno>
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<author role="aut"> <persName> <forename type="first">Fritz</forename>
<surname>Poustka</surname>
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<idno type="halauthorid">483797</idno>
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<author role="aut"> <persName> <forename type="first">Jiannis</forename>
<surname>Ragoussis</surname>
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<idno type="halauthorid">529496</idno>
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<author role="aut"> <persName> <forename type="first">Regina</forename>
<surname>Regan</surname>
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<idno type="halauthorid">529414</idno>
<affiliation ref="#struct-128862"></affiliation>
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<author role="aut"> <persName> <forename type="first">Wendy</forename>
<surname>Roberts</surname>
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<idno type="halauthorid">529499</idno>
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<author role="aut"> <persName> <forename type="first">Kathryn</forename>
<surname>Roeder</surname>
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<idno type="halauthorid">529500</idno>
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<author role="aut"> <persName> <forename type="first">Bernadette</forename>
<surname>Roge</surname>
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<idno type="halauthorid">529501</idno>
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<author role="aut"> <persName> <forename type="first">Michael</forename>
<forename type="middle">L.</forename>
<surname>Rutter</surname>
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<idno type="halauthorid">529502</idno>
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<author role="aut"> <persName> <forename type="first">Sabine</forename>
<surname>Schlitt</surname>
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<idno type="halauthorid">483800</idno>
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<author role="aut"> <persName> <forename type="first">Naisha</forename>
<surname>Shah</surname>
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<idno type="halauthorid">529510</idno>
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<author role="aut"> <persName> <forename type="first">Val</forename>
<forename type="middle">C.</forename>
<surname>Sheffield</surname>
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<idno type="halauthorid">529511</idno>
<affiliation ref="#struct-128982"></affiliation>
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<author role="aut"> <persName> <forename type="first">Latha</forename>
<surname>Soorya</surname>
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<idno type="halauthorid">396592</idno>
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<author role="aut"> <persName> <forename type="first">Inês</forename>
<surname>Sousa</surname>
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<author role="aut"> <persName> <forename type="first">Vera</forename>
<surname>Stoppioni</surname>
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<idno type="halauthorid">529515</idno>
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<author role="aut"> <persName> <forename type="first">Nuala</forename>
<surname>Sykes</surname>
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<author role="aut"> <persName> <forename type="first">Raffaella</forename>
<surname>Tancredi</surname>
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<idno type="halauthorid">529517</idno>
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<author role="aut"> <persName> <forename type="first">Ann</forename>
<forename type="middle">P.</forename>
<surname>Thompson</surname>
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<idno type="halauthorid">529520</idno>
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<author role="aut"> <persName> <forename type="first">Susanne</forename>
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<idno type="halauthorid">529521</idno>
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<author role="aut"> <persName> <forename type="first">Ana</forename>
<surname>Tryfon</surname>
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<author role="aut"> <persName> <forename type="first">John</forename>
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<idno type="halauthorid">529523</idno>
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<author role="aut"> <persName> <forename type="first">Herman</forename>
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<author role="aut"> <persName> <forename type="first">John</forename>
<forename type="middle">B.</forename>
<surname>Vincent</surname>
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<idno type="halauthorid">529524</idno>
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<author role="aut"> <persName> <forename type="first">Fred</forename>
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<author role="aut"> <persName> <forename type="first">Jacob</forename>
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<author role="aut"> <persName> <forename type="first">Simon</forename>
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<author role="aut"> <persName> <forename type="first">Kerstin</forename>
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<author role="aut"> <persName> <forename type="first">Shawn</forename>
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<author role="aut"> <persName> <forename type="first">Danielle</forename>
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<author role="aut"> <persName> <forename type="first">Lonnie</forename>
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<author role="aut"> <persName> <forename type="first">Anthony</forename>
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<author role="aut"> <persName> <forename type="first">Agatino</forename>
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<idno type="halauthorid">304095</idno>
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<author role="aut"> <persName> <forename type="first">Rita</forename>
<forename type="middle">M.</forename>
<surname>Cantor</surname>
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<idno type="halauthorid">529537</idno>
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<author role="aut"> <persName> <forename type="first">Hilary</forename>
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<idno type="halauthorid">529539</idno>
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<author role="aut"> <persName> <forename type="first">Michael</forename>
<forename type="middle">L.</forename>
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<author role="aut"> <persName> <forename type="first">Geraldine</forename>
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<idno type="halauthorid">529436</idno>
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<author role="aut"> <persName> <forename type="first">Sean</forename>
<surname>Ennis</surname>
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<author role="aut"> <persName> <forename type="first">Christine</forename>
<forename type="middle">M.</forename>
<surname>Freitag</surname>
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<idno type="halauthorid">529444</idno>
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<author role="aut"> <persName> <forename type="first">Daniel</forename>
<forename type="middle">H.</forename>
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<author role="aut"> <persName> <forename type="first">Jonathan</forename>
<forename type="middle">L.</forename>
<surname>Haines</surname>
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<idno type="halauthorid">529545</idno>
<affiliation ref="#struct-128988"></affiliation>
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<author role="aut"> <persName> <forename type="first">Sabine</forename>
<forename type="middle">M.</forename>
<surname>Klauck</surname>
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<author role="aut"> <persName> <forename type="first">William</forename>
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<idno type="halauthorid">529477</idno>
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<author role="aut"> <persName> <forename type="first">Judith</forename>
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<author role="aut"> <persName> <forename type="first">Anthony</forename>
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<author role="aut"> <persName> <forename type="first">Stanley</forename>
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<author role="aut"> <persName> <forename type="first">John</forename>
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<author role="aut"> <persName> <forename type="first">Margaret</forename>
<forename type="middle">A.</forename>
<surname>Pericak-Vance</surname>
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<author role="aut"> <persName> <forename type="first">Joseph</forename>
<surname>Piven</surname>
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<idno type="halauthorid">529492</idno>
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<author role="aut"> <persName> <forename type="first">Gerard</forename>
<forename type="middle">D.</forename>
<surname>Schellenberg</surname>
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<idno type="halauthorid">529552</idno>
<affiliation ref="#struct-128989"></affiliation>
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<author role="aut"> <persName> <forename type="first">Stephen</forename>
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<author role="aut"> <persName> <forename type="first">Astrid</forename>
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<idno type="halauthorid">529554</idno>
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<author role="aut"> <persName> <forename type="first">Thomas</forename>
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<author role="aut"> <persName> <forename type="first">Ellen</forename>
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<author role="aut"> <persName> <forename type="first">Joseph</forename>
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<author role="aut"> <persName> <forename type="first">Edwin</forename>
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<author role="aut"> <persName> <forename type="first">Michael</forename>
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<author role="aut"> <persName> <forename type="first">Joachim</forename>
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<author role="aut"> <persName> <forename type="first">Andrew</forename>
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<forename type="middle">S.</forename>
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<author role="aut"> <persName> <forename type="first">Peter</forename>
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<idno type="halauthorid">529553</idno>
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<author role="aut"> <persName> <forename type="first">Veronica</forename>
<forename type="middle">J.</forename>
<surname>Vieland</surname>
</persName>
<idno type="halauthorid">529555</idno>
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<author role="aut"> <persName> <forename type="first">Hakon</forename>
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<idno type="halauthorid">528993</idno>
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<surname>Devlin</surname>
</persName>
<email type="md5">d78e39c69074b1a497c15e0472f4684b</email>
<email type="domain">upmc.edu</email>
<idno type="halauthorid">529570</idno>
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<editor role="depositor"> <persName> <forename>Catalina</forename>
<surname>Betancur</surname>
</persName>
<email type="md5">8eb223d47e4d8556ca73792b6172fe6c</email>
<email type="domain">inserm.fr</email>
</editor>
</titleStmt>
<editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2012-08-12 14:37:08</date>
<date type="whenModified">2017-11-10 10:42:02</date>
<date type="whenReleased">2012-11-05 10:43:30</date>
<date type="whenProduced">2012-11-01</date>
<date type="whenEndEmbargoed">2012-08-12</date>
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<author role="aut"> <persName> <forename type="first">Daniel</forename>
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<author role="aut"> <persName> <forename type="first">Sabine</forename>
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<author role="aut"> <persName> <forename type="first">William</forename>
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<author role="aut"> <persName> <forename type="first">Anthony</forename>
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<author role="aut"> <persName> <forename type="first">Stanley</forename>
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<author role="aut"> <persName> <forename type="first">John</forename>
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<idno type="issn">0964-6906</idno>
<idno type="eissn">1460-2083</idno>
<title level="j">Human Molecular Genetics</title>
<imprint> <publisher>Oxford University Press (OUP)</publisher>
<biblScope unit="volume">21</biblScope>
<biblScope unit="issue">21</biblScope>
<biblScope unit="pp">4781-92</biblScope>
<date type="datePub">2012-11-01</date>
<date type="dateEpub">2012-07-26</date>
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<idno type="doi">10.1093/hmg/dds301</idno>
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<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.</abstract>
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