Individual common variants exert weak effects on the risk for autism spectrum disorders.
Richard Anney,Lambertus Klei,Dalila Pinto,Dalila Pinto,Joana Almeida,Elena Bacchelli,Gillian Baird,Nadia Bolshakova,Sven Bölte,Patrick Bolton,Thomas Bourgeron,Thomas Bourgeron,Sean Brennan,Jessica Brian,Jillian P. Casey,Judith Conroy,Catarina Correia,Catarina Correia,Christina Corsello,Emily L. Crawford,Maretha de Jonge,Richard Delorme,Eftichia Duketis,Frederico Duque,Annette Estes,Penny Farrar,Bridget A. Fernandez,Susan E. Folstein,Eric Fombonne,John R. Gilbert,Christopher Gillberg,Joseph T. Glessner,Andrew Green,Jonathan Green,Stephen J. Guter,Elizabeth A. Heron,Richard Holt,Jennifer L. Howe,Gillian Hughes,Vanessa Hus,Roberta Igliozzi,Suma Jacob,Graham Kenny,Cecilia Kim,Alexander Kolevzon,Vlad Kustanovich,Clara Lajonchere,Janine A. Lamb,Miriam Law-Smith,Marion Leboyer,Ann Le Couteur,Bennett L. Leventhal,Bennett L. Leventhal,Xiao-Qing Liu,Frances Lombard,Catherine Lord,Linda Lotspeich,Sabata C. Lund,Tiago R. Magalhaes,Tiago R. Magalhaes,Carine Mantoulan,Christopher J. McDougle,Christopher J. McDougle,Nadine M. Melhem,Alison K. Merikangas,Nancy J. Minshew,Ghazala Mirza,Jeff Munson,Carolyn Noakes,Gudrun Nygren,Katerina Papanikolaou,Alistair T. Pagnamenta,Barbara Parrini,Tara Paton,Andrew Pickles,David J. Posey,Fritz Poustka,Jiannis Ragoussis,Regina Regan,Wendy Roberts,Kathryn Roeder,Bernadette Rogé,Michael Rutter,Sabine Schlitt,Naisha Shah,Val C. Sheffield,Latha Soorya,Inês Sousa,Vera Stoppioni,Nuala Sykes,Raffaella Tancredi,Ann P. Thompson,Susanne Thomson,Ana Tryfon,John Tsiantis,Herman van Engeland,John B. Vincent,Fred R. Volkmar,Jacob A. S. Vorstman,Simon Wallace,Kirsty Wing,Kerstin Wittemeyer,Shawn Wood,Danielle Zurawiecki,Lonnie Zwaigenbaum,Anthony J. Bailey,Agatino Battaglia,Rita M. Cantor,Hilary Coon,Michael L. Cuccaro,Geraldine Dawson,Geraldine Dawson,Sean Ennis,Christine M. Freitag,Daniel H. Geschwind,Jonathan L. Haines,Sabine M. Klauck,William M. McMahon,Elena Maestrini,Judith Miller,Judith Miller,Anthony P. Monaco,Anthony P. Monaco,Stanley F. Nelson,John I. Nurnberger,Guiomar Oliveira,Jeremy R. Parr,Margaret A. Pericak-Vance,Joseph Piven,Gerard D. Schellenberg,Stephen W. Scherer,Astrid M. Vicente,Astrid M. Vicente,Thomas H. Wassink,Ellen M. Wijsman,Catalina Betancur,Catalina Betancur,Catalina Betancur,Joseph D. Buxbaum,Edwin H. Cook,Louise Gallagher,Michael Gill,Joachim Hallmayer,Andrew D. Paterson,James S. Sutcliffe,Peter Szatmari,Veronica J. Vieland,Hakon Hakonarson,Bernie Devlin +148 more
TLDR
Stage 2 of the Autism Genome Project genome-wide association study is reported, adding 1301 ASD families and bringing the total to 2705 families analysed, and it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.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.read more
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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
S. Hong Lee,Stephan Ripke,Stephan Ripke,Benjamin M. Neale,Benjamin M. Neale,Stephen V. Faraone,Shaun Purcell,Shaun Purcell,Shaun Purcell,Roy H. Perlis,Roy H. Perlis,Bryan J. Mowry,Bryan J. Mowry,Anita Thapar,Michael E. Goddard,John S. Witte,Devin Absher,Ingrid Agartz,Huda Akil,Farooq Amin,Ole A. Andreassen,Adebayo Anjorin,Richard Anney,Verneri Anttila,Dan E. Arking,Philip Asherson,Maria Helena Pinto de Azevedo,Lena Backlund,Judith A. Badner,Anthony J. Bailey,Tobias Banaschewski,Jack D. Barchas,Michael R. Barnes,Thomas B. Barrett,Nicholas Bass,Agatino Battaglia,Michael Bauer,Mònica Bayés,Frank Bellivier,Sarah E. Bergen,Sarah E. Bergen,Sarah E. Bergen,Wade H. Berrettini,Catalina Betancur,Catalina Betancur,Catalina Betancur,Thomas Bettecken,Joseph Biederman,Elisabeth B. Binder,Donald W. Black,Douglas Blackwood,Cinnamon S. Bloss,Michael Boehnke,Dorret I. Boomsma,Gerome Breen,Gerome Breen,René Breuer,Richard Bruggeman,Paul Cormican,Nancy G. Buccola,Jan K. Buitelaar,William E. Bunney,Joseph D. Buxbaum,William Byerley,Enda M. Byrne,Sian Caesar,Wiepke Cahn,Rita M. Cantor,Miguel Casas,Aravinda Chakravarti,Kimberly Chambert,Khalid Choudhury,Sven Cichon,Sven Cichon,C. Robert Cloninger,David A. Collier,Edwin H. Cook,Hilary Coon,Bru Cormand,Aiden Corvin,William Coryell,David Craig,Ian W. Craig,Jennifer Crosbie,Michael L. Cuccaro,David Curtis,Darina Czamara,Susmita Datta,Geraldine Dawson,Richard O. Day,Eco J. C. de Geus,Franziska Degenhardt,Srdjan Djurovic,Gary Donohoe,Alysa E. Doyle,Jubao Duan,Frank Dudbridge,Eftichia Duketis,Richard P. Ebstein,Howard J. Edenberg,Josephine Elia,Sean Ennis,Bruno Etain,Ayman H. Fanous,Ayman H. Fanous,Anne Farmer,I. Nicol Ferrier,Matthew Flickinger,Eric Fombonne,Tatiana Foroud,Josef Frank,Barbara Franke,Christine Fraser,Robert Freedman,Nelson B. Freimer,Christine M. Freitag,Marion Friedl,Louise Frisén,Louise Gallagher,Pablo V. Gejman,Lyudmila Georgieva,Elliot S. Gershon,Daniel H. Geschwind,Ina Giegling,Michael Gill,Scott D. 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Potash,Fritz Poustka,Peter Propping,Vinay Puri,Digby Quested,Emma M. Quinn,Josep Antoni Ramos-Quiroga,Henrik B. Rasmussen,Soumya Raychaudhuri,Soumya Raychaudhuri,Karola Rehnström,Andreas Reif,Marta Ribasés,John P. Rice,Marcella Rietschel,Kathryn Roeder,Herbert Roeyers,Lizzy Rossin,Aribert Rothenberger,Guy A. Rouleau,Douglas M. Ruderfer,Dan Rujescu,Alan R. Sanders,Stephen Sanders,Susan L. Santangelo,Susan L. Santangelo,Joseph A. Sergeant,Russell Schachar,Martin Schalling,Alan F. Schatzberg,William A. Scheftner,Gerard D. Schellenberg,Stephen W. Scherer,Nicholas J. Schork,Thomas G. Schulze,Thomas G. Schulze,Johannes Schumacher,Markus J. Schwarz,Edward M. Scolnick,Laura J. Scott,Jianxin Shi,Paul D. Shilling,Stanley I. Shyn,Jeremy M. Silverman,Susan L. Slager,Susan L. Smalley,Johannes H. Smit,Erin N. Smith,Edmund J.S. Sonuga-Barke,Edmund J.S. Sonuga-Barke,David St Clair,Matthew W. State,Michael Steffens,Hans-Christoph Steinhausen,Hans-Christoph Steinhausen,Hans-Christoph Steinhausen,John Strauss,Jana Strohmaier,T. Scott Stroup,James S. Sutcliffe,Peter Szatmari,Szabocls Szelinger,Srinivasa Thirumalai,Robert C. Thompson,Alexandre A. Todorov,Federica Tozzi,Jens Treutlein,Manfred Uhr,Edwin J. C. G. van den Oord,Gerard van Grootheest,Jim van Os,Astrid M. Vicente,Astrid M. Vicente,Astrid M. Vicente,Veronica J. Vieland,John B. Vincent,Peter M. Visscher,Christopher A. Walsh,Thomas H. Wassink,Stanley J. Watson,Myrna M. Weissman,Thomas Werge,Thomas F. Wienker,Ellen M. Wijsman,Gonneke Willemsen,Nigel Williams,A. Jeremy Willsey,Stephanie H. Witt,Wei Xu,Allan H. Young,Allan H. Young,Timothy W. Yu,Stanley Zammit,Peter P. Zandi,Peng Zhang,Frans G. Zitman,Sebastian Zöllner,Bernie Devlin,John R. Kelsoe,John R. Kelsoe,Pamela Sklar,Mark J. Daly,Mark J. Daly,Michael Conlon O'Donovan,Nicholas John Craddock,Patrick F. Sullivan,Jordan W. Smoller,Jordan W. Smoller,Kenneth S. Kendler,Naomi R. Wray +405 more
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Journal ArticleDOI
Identification of common genetic risk variants for autism spectrum disorder
TL;DR: A genome-wide association meta-analysis of 18,381 austim spectrum disorder cases and 27,969 controls identifies five risk loci and the authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.
Journal ArticleDOI
Most genetic risk for autism resides with common variation
Trent Gaugler,Lambertus Klei,Stephen Sanders,Corneliu A. Bodea,Arthur P. Goldberg,Ann B. Lee,Milind Mahajan,Dina Manaa,Yudi Pawitan,Jennifer Reichert,Stephan Ripke,Sven Sandin,Pamela Sklar,Oscar Svantesson,Abraham Reichenberg,Christina M. Hultman,Bernie Devlin,Kathryn Roeder,Joseph D. Buxbaum +18 more
TL;DR: Autism's genetic architecture is reached: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.
Journal ArticleDOI
Integrative Functional Genomic Analyses Implicate Specific Molecular Pathways and Circuits in Autism
Neelroop N. Parikshak,Rui Luo,Alice Zhang,Hyejung Won,Jennifer K. Lowe,Vijayendran Chandran,Steve Horvath,Daniel H. Geschwind +7 more
TL;DR: It is shown that the patterns of ASD and ID risk genes are distinct, providing a biological framework for further investigating the pathophysiology of ASD.
Journal ArticleDOI
Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders
Dalila Pinto,Elsa Delaby,Elsa Delaby,Elsa Delaby,Daniele Merico,Mafalda Barbosa,Alison K. Merikangas,Lambertus Klei,Bhooma Thiruvahindrapuram,Xiao Xu,Robert Ziman,Zhuozhi Wang,Jacob A. S. Vorstman,Ann P. Thompson,Regina Regan,Regina Regan,Marion Pilorge,Marion Pilorge,Marion Pilorge,Giovanna Pellecchia,Alistair T. Pagnamenta,Bárbara Oliveira,Bárbara Oliveira,Christian R. Marshall,Tiago R. Magalhaes,Tiago R. Magalhaes,Jennifer K. Lowe,Jennifer L. Howe,Anthony J. Griswold,John R. Gilbert,Eftichia Duketis,Beth A. Dombroski,Maretha de Jonge,Michael L. Cuccaro,Emily L. Crawford,Catarina Correia,Catarina Correia,Judith Conroy,Inȇs C. Conceição,Inȇs C. Conceição,Andreas G. Chiocchetti,Jillian P. Casey,Jillian P. Casey,Guiqing Cai,Christelle Cabrol,Christelle Cabrol,Christelle Cabrol,Nadia Bolshakova,Elena Bacchelli,Richard Anney,Steven Gallinger,Michelle Cotterchio,Graham Casey,Lonnie Zwaigenbaum,Kerstin Wittemeyer,Kirsty Wing,Simon Wallace,Herman van Engeland,Ana Tryfon,Susanne Thomson,Latha Soorya,Bernadette Rogé,Wendy Roberts,Fritz Poustka,Susana Mouga,Nancy J. Minshew,L. Alison McInnes,Susan G. McGrew,Catherine Lord,Marion Leboyer,Ann Le Couteur,Alexander Kolevzon,Patricia Jiménez González,Suma Jacob,Suma Jacob,Richard Holt,Stephen J. Guter,Jonathan Green,Andrew Green,Andrew Green,Christopher Gillberg,Bridget A. Fernandez,Frederico Duque,Richard Delorme,Geraldine Dawson,Pauline Chaste,Cátia Café,Sean Brennan,Thomas Bourgeron,Patrick Bolton,Patrick Bolton,Sven Bölte,Raphael Bernier,Gillian Baird,Anthony J. Bailey,Evdokia Anagnostou,Joana Almeida,Ellen M. Wijsman,Veronica J. Vieland,Astrid M. Vicente,Astrid M. Vicente,Gerard D. Schellenberg,Margaret A. Pericak-Vance,Andrew D. Paterson,Jeremy R. Parr,Guiomar Oliveira,John I. Nurnberger,Anthony P. Monaco,Anthony P. Monaco,Elena Maestrini,Sabine M. Klauck,Hakon Hakonarson,Jonathan L. Haines,Daniel H. Geschwind,Christine M. Freitag,Susan E. Folstein,Sean Ennis,Sean Ennis,Hilary Coon,Agatino Battaglia,Peter Szatmari,James S. Sutcliffe,Joachim Hallmayer,Michael Gill,Edwin H. Cook,Joseph D. Buxbaum,Bernie Devlin,Louise Gallagher,Catalina Betancur,Catalina Betancur,Catalina Betancur,Stephen W. Scherer +131 more
TL;DR: For example, the authors analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability.
References
More filters
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders
TL;DR: The revised interview has been reorganized, shortened, modified to be appropriate for children with mental ages from about 18 months into adulthood and linked to ICD-10 and DSM-IV criteria.
Journal ArticleDOI
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
Shaun Purcell,Shaun Purcell,Naomi R. Wray,Jennifer Stone,Jennifer Stone,Peter M. Visscher,Michael Conlon O'Donovan,Patrick F. Sullivan,Pamela Sklar,Pamela Sklar,Douglas M. Ruderfer,Andrew McQuillin,Derek W. Morris,Colm O'Dushlaine,Aiden Corvin,Peter Holmans,Stuart MacGregor,Hugh Gurling,Douglas Blackwood,Nicholas John Craddock,Michael Gill,Christina M. Hultman,Christina M. Hultman,George Kirov,Paul Lichtenstein,Walter J. Muir,Michael John Owen,Carlos N. Pato,Edward M. Scolnick,Edward M. Scolnick,David St Clair,Nigel Williams,Lyudmila Georgieva,Ivan Nikolov,Nadine Norton,Hywel Williams,Draga Toncheva,Vihra Milanova,Emma Flordal Thelander,Patrick Sullivan,Elaine Kenny,Emma M. Quinn,Khalid Choudhury,Susmita Datta,Jonathan Pimm,Srinivasa Thirumalai,Vinay Puri,Robert Krasucki,Jacob Lawrence,Digby Quested,Nicholas Bass,Caroline Crombie,Gillian Fraser,Soh Leh Kuan,Nicholas Walker,Kevin A. McGhee,Ben S. Pickard,P. Malloy,Alan W Maclean,Margaret Van Beck,Michele T. Pato,Helena Medeiros,Frank A. Middleton,Célia Barreto Carvalho,Christopher P. Morley,Ayman H. Fanous,David V. Conti,James A. Knowles,Carlos Ferreira,António Macedo,M. Helena Azevedo,Andrew Kirby,Andrew Kirby,Manuel A. R. Ferreira,Manuel A. R. Ferreira,Mark J. Daly,Mark J. Daly,Kimberly Chambert,Finny G Kuruvilla,Stacey Gabriel,Kristin G. Ardlie,Jennifer L. Moran +81 more
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Journal ArticleDOI
Strong Association of De Novo Copy Number Mutations with Autism
Jonathan Sebat,B. Lakshmi,Dheeraj Malhotra,Jennifer Troge,Christa Lese-Martin,Tom Walsh,Boris Yamrom,Seungtai Yoon,Alexander Krasnitz,Jude Kendall,Anthony Leotta,Deepa Pai,Ray Zhang,Yoon-ha Lee,James W. Hicks,Sarah J. Spence,Annette Lee,Kaija Puura,Terho Lehtimäki,David H. Ledbetter,Peter K. Gregersen,Joel D. Bregman,James S. Sutcliffe,Vaidehi Jobanputra,Wendy K. Chung,Dorothy Warburton,Mary Claire King,David Skuse,Daniel H. Geschwind,T. Conrad Gilliam,Kenny Ye,Michael Wigler +31 more
TL;DR: Findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.
Journal ArticleDOI
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
Brian J. O'Roak,Laura Vives,Santhosh Girirajan,Emre Karakoc,Niklas Krumm,Bradley P. Coe,Roie Levy,Arthur Ko,Choli Lee,Joshua D. Smith,Emily H. Turner,Ian B. Stanaway,Benjamin Vernot,Maika Malig,Carl Baker,Beau Reilly,Joshua M. Akey,Elhanan Borenstein,Elhanan Borenstein,Mark J. Rieder,Deborah A. Nickerson,Raphael Bernier,Jay Shendure,Evan E. Eichler,Evan E. Eichler +24 more
TL;DR: It is shown that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD.
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