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A genome-wide linkage and association scan reveals novel loci for autism

Nature volume 461, pages 802–808 (2009)Cite this article

Abstract

Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success1. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 × 10-7). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

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Figure 1: Genome-wide linkage results.
Figure 2: SEMA5A expression in autism brains.

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Acknowledgements

We thank all of the families who have participated in and contributed to the public resources that we have used in these studies. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources. The Gene Discovery Project of Johns Hopkins was funded by grants from the National Institutes of Mental Health (MH60007, MH081754) and the Simons Foundation. This study was funded in part through a grant from the Autism Consortium of Boston. Support for the Extreme Discordant Sib-Pair (EDSP) family sample was provided by the NLM Family foundation. Support for the Massachusetts General Hospital (MGH)–Finnish collaborative sample was provided by NARSAD. Support for the Homozygosity Mapping Collaborative for Autism (HMCA) came from NIMH (1R01 MH083565), the Nancy Lurie Marks (NLM) Family Foundation and the Simons Foundation. Eric M. Morrow is supported by the NIMH (1K23MH080954). Support for the Iranian family sample was provided by the Special Education Organization of Iran, under the Iranian Ministry of Education. Lauren A. Weiss was supported by a Ruth L. Kirschstein National Research Service Award and is currently supported by the International Mental Health Research Organization. The collection of data and biomaterials that participated in the National Institute of Mental Health (NIMH) Autism Genetics Initiative has been supported by National Institute of Health grants MH52708, MH39437, MH00219 and MH00980; National Health Medical Research Council grant 0034328; and by grants from the Scottish Rite, the Spunk Fund, Inc., the Rebecca and Solomon Baker Fund, the APEX Foundation, the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD), and the endowment fund of the Nancy Pritzker Laboratory (Stanford); and by gifts from the Autism Society of America, the Janet M. Grace Pervasive Developmental Disorders Fund, and families and friends of individuals with autism. The NIMH collection Principal Investigators and Co-Investigators were: Neil Risch, Richard M. Myers, Donna Spiker, Linda J. Lotspeich, Joachim F. Hallmayer, Helena C. Kraemer, Roland D. Ciaranello, Luigi Luca Cavalli-Sforza (Stanford University, Stanford); William M. McMahon and P. Brent Petersen (University of Utah, Salt Lake City). The Stanford team is indebted to the parent groups and clinician colleagues who referred families and extends their gratitude to the families with individuals with autism who were partners in this research. The collection data and biomaterials also come from the Autism Genetic Resource Exchange (AGRE) collection. This program has been supported by a National Institute of Health grant MH64547 and the Cure Autism Now Foundation. The AGRE collection Principal Investigator is Daniel H. Geschwind (UCLA). The Co-Principal Investigators include Stanley F. Nelson and Rita M. Cantor (UCLA), Christa Lese Martin (Univ. Chicago), T. Conrad Gilliam (Columbia). Co-Investigators include Maricela Alarcon (UCLA), Kenneth Lange (UCLA), Sarah J. Spence (UCLA), David H. Ledbetter (Emory) and Hank Juo (Columbia). Scientific oversight of the AGRE program is provided by a steering committee (Chair: Daniel H. Geschwind; Members: W. Ted Brown, Maja Bucan, Joseph D. Buxbaum, T. Conrad Gilliam, David Greenberg, David H. Ledbetter, Bruce Miller, Stanley F. Nelson, Jonathan Pevsner, Carol Sprouse, Gerard D. Schellenberg and Rudolph Tanzi). The Autism Genome Project (AGP) work was supported by the following grants: (1) The Hilibrand Foundation (Principal Investigator Joachim F. Hallmayer); (2) Autism Speaks (for the AGP); (3) grants from the National Institutes of Health (NIH) MH61009 (James S. Sutcliffe), MH55135 (Susan E. Folstein), MH55284 (Joseph Piven), HD055782 (Ellen M. Wijsman), NS042165 (Joachim F. Hallmayer); (4) Fundação para a Ciência e Tecnologia (POCTI/39636/ESP/2001) Fundação Calouste Gulbenkian (Astrid Vincente); (5) INSERM, Fondation de France, Fondation Orange, Fondation pour la Recherche Médicale (Catalina Betancur, Marion Leboyer), and the Swedish Science Council (Christopher Gillberg); (6) The Seaver Foundation (Joseph D. Buxbaum); (7) The Children’s Medical & Research Foundation (CMRF), Our Lady’s Children’s Hospital, Crumlin, Ireland (Sean Ennis); (8) The Medical Research Council (MRC) (Anthony P. Monaco, Anthony J. Bailey). Fresh-frozen brain tissue samples were obtained through the Autism Tissue Program and the Harvard Brain Bank.

Author Contributions L.A.W., D.E.A., M.J.D. and A. Chakravarti led design and execution of joint scan analyses and manuscript writing. Johns Hopkins University–NIMH genome scan team: D.E.A. and A. Chakravarti led study design and analysis of scan; C.W.B. and E.H.C. provided evaluation of phenotype data, phenotype definition from primary data and editing of the manuscript; K. West, A.O’C. and G.H. conducted primary and replication genotyping with allele calling; R.L.T. and A.B.W. performed expression analysis and editing of the manuscript. Autism Consortium–AGRE genome scan team: L.A.W., T.G. and M.J.D. performed data processing and analysis for the genome-wide association scan; S-C.C., E.M.H., E.M.M., R.S. and S.L.S. provided evaluation of phenotype data and phenotype definition from primary data; S.G., C. Gates, C. Sougnez and C. Stevens led the genotyping team; A.K., J.K., F.K., S.M., B.N. and S.P. performed and evaluated allele calling and advised the analysis; M.J.D., L.A.W., R.T., P.S., S.L.S., J. Gusella and D.A. designed and initiated the study and provided manuscript comments and edits. Replication teams: each replication team provided genotypes, phenotypes and analysis of top ranking SNPs from the combined genome-wide association scan and contributed comments during manuscript preparation.

Author information

Author notes

  1. Lauren A. Weiss

    Present address: Present addresses: Department of Psychiatry, Institute for Human Genetics, Center for Neurobiology and Psychiatry, UCSF, San Francisco, California, USA (L.A.W.); Department of Molecular Biology, Cell Biology and Biochemistry, and Institute for Brain Science, Brown University, Providence, Rhode Island, USA (E.M.M.).,

  2. Annemarie Poustka: Deceased.

  3. Lauren A. Weiss and Dan E. Arking: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.,

    Lauren A. Weiss, Mark J. Daly, Lauren A. Weiss, Todd Green, Shun-Chiao Chang, Andrew Kirby, Joshua Korn, Finny Kuruvilla, Steven McCarroll, Eric M. Morrow, Benjamin Neale, Shaun Purcell, Roksana Sasanfar, David Altshuler, James Gusella, Susan L. Santangelo, Pamela Sklar, Rudolph Tanzi, Mark J. Daly, Eric M. Morrow, David Pauls, Roksana Sasanfar, Susan L. Santangelo, Kara Andresen, Brian Winkloski & Stephen Haddad

  2. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.,

    Lauren A. Weiss, Mark J. Daly, Lauren A. Weiss, Todd Green, Stacey Gabriel, Casey Gates, Andrew Kirby, Joshua Korn, Finny Kuruvilla, Steven McCarroll, Eric M. Morrow, Benjamin Neale, Shaun Purcell, Carrie Sougnez, Christine Stevens, David Altshuler, James Gusella, Pamela Sklar, Mark J. Daly, Eric M. Morrow, Seung-Yun Yoo, Robert Sean Hill & Christopher A. Walsh

  3. Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.,

    Dan E. Arking, Aravinda Chakravarti, Dan E. Arking, Kristen West, Ashley O’Connor, Gina Hilton & Aravinda Chakravarti

  4. Department of Psychiatry, Institute for Juvenile Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA.,

    Camille W. Brune, Edwin H. Cook Jr, Stephen J. Guter, Bennett L. Leventhal, Nancy J. Minshew & Jeff Salt

  5. Center for Neurodegeneration and Experimental Therapeutics, University of Alabama School of Medicine, Birmingham, Alabama 35294, USA.,

    Rebecca L. Tomlinson, Andrew B. West, Ellen M. Hanson & Edwin H. Cook Jr

  6. Developmental Medicine Center, Children’s Hospital Boston, Boston, Massachusetts 02115, USA.,

    Janice Ware, Elaine LeClair, Ellen M. Hanson, Rachel Hundley & Leonard A. Rappaport

  7. Division of Genetics, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.,

    Eric M. Morrow, Eric M. Morrow, Seung-Yun Yoo, Robert Sean Hill, Jennifer N. Partlow, Brenda Barry, Christopher A. Walsh, Lou Kunkel, Zak Kohane, Tram Tran, Sek Won Kong, Stephanie Brewster O’Neil, Ingrid Holm, Heather Peters, Elizabeth Baroni, Aislyn Cangialose, Lindsay Jackson, Lisa Albers, Ronald Becker, Carolyn Bridgemohan, Sandra Friedman, Kerim Munir, Ramzi Nazir, Judith Palfrey, Alison Schonwald & Esau Simmons

  8. Special Education Organization, Tehran, Iran.,

    Roksana Sasanfar, Roksana Sasanfar, Ala Tolouei, Majid Ghadami, Azam Hosseinipour & Maryam Valujerdi

  9. Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford OX3 7JX, UK.,

    Anthony J. Bailey, Magdalena Laskawiec, Jeremy R. Parr, Katy Renshaw & Simon Wallace

  10. Newcomen Centre, Guy’s Hospital, London SE1 9RT, UK.,

    Gillian Baird

  11. Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital and The Ohio State University, Columbus, Ohio 43205, USA.,

    Veronica J. Vieland

  12. Child and Adolescent Mental Health, University of Newcastle, Sir James Spence Institute, Newcastle upon Tyne NE1 4LP, UK.,

    Tom Berney, Ann Le Couteur & Helen McConachie

  13. INSERM U952, Université Pierre et Marie Curie, 75005 Paris, France.,

    Catalina Betancur

  14. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, J.W. Goethe University Frankfurt, 60528 Frankfurt, Germany.,

    Sven Bölte, Eftichia Duketis, Christine M. Freitag & Fritz Poustka

  15. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, London SE5 8AF, UK.,

    Patrick F. Bolton

  16. Autism Research Unit, The Hospital for Sick Children and Bloorview Kids Rehabilitation, University of Toronto, Toronto, Ontario M5G 1Z8, Canada.,

    Jessica Brian, Xiao-Qing Liu, Andrew D. Paterson & Wendy Roberts

  17. Department of Pediatrics and Psychology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada.,

    Susan E. Bryson

  18. Departments of Psychiatry, Laboratory of Molecular Neuropsychiatry, Seaver Autism Center for Research and Treatment, Genetics and Genomic Sciences, and Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.,

    Joseph D. Buxbaum, Guiqing Cai & Jennifer Reichert

  19. Department of Human Genetics, University of California–Los Angeles School of Medicine, Los Angeles, California 90095, USA.,

    Rita M. Cantor

  20. Psychiatry Department, University of Utah Medical School, Salt Lake City, Utah 84108, USA.,

    Hilary Coon, William M. McMahon & Judith Miller

  21. Autism and Communicative Disorders Centre, University of Michigan, Ann Arbor, Michigan 48104, USA.,

    Christina Corsello, Vanessa Hus & Catherine Lord

  22. Miami Institute for Human Genomics, University of Miami, Miami, Florida 33136, USA.,

    Michael L. Cuccaro, John Gilbert & Margaret A. Pericak-Vance

  23. Departments of Psychology and Psychiatry, University of Washington, Seattle, Washington 98195, USA.,

    Annette Estes & Jeff Munson

  24. Department of Child Psychiatry, University Medical Center, Utrecht 3508 GA, The Netherlands.,

    Maretha de Jonge & Herman Van Engeland

  25. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 19104-6100, USA.,

    Bernie Devlin

  26. School of Medicine and Medical Science University College, Dublin 4, Ireland.,

    Judith Conroy, Sean Ennis, Andrew Green & Regina Regan

  27. Division of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada.,

    Eric Fombonne, Ridha Joober & Eric Fombonne

  28. Department of Psychiatry, Autism Genetics Group, School of Medicine, Trinity College, Dublin 8, Ireland.,

    Richard Anney, Louise Gallagher, Michael Gill & Katherine Tansey

  29. Department of Neurology, University of California–Los Angeles School of Medicine, Los Angeles, California 90095, USA.,

    Daniel H. Geschwind

  30. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.,

    Jeremy Goldberg, Peter Szatmari & Ann P. Thompson

  31. Academic Department of Child Psychiatry, Booth Hall of Children’s Hospital, Blackley, Manchester M9 7AA, UK.,

    Jonathan Green

  32. Centre for Human Genetics Research, Vanderbilt University Medical Centre, Nashville, Tennessee 37232, USA.,

    Jonathan L. Haines

  33. Child and Adolescent Psychiatry and Child Development, Stanford University School of Medicine, Stanford, California 94304, USA.,

    Joachim F. Hallmayer & Linda J. Lotspeich

  34. Deutsches Krebsforschungszentrum, Molekulare Genomanalyse, 69120 Heidelberg, Germany.,

    Sabine M. Klauck & Annemarie Poustka

  35. Centre for Integrated Genomic Medical Research, University of Manchester, Manchester M13 9PT, UK.,

    Janine A. Lamb

  36. Department of Pediatrics, McMaster University, Hamilton, Ontario L8S 3Z5, Canada.,

    William Mahoney

  37. Centre d’Eudes et de Recherches en Psychopathologie, University de Toulouse Le Miral, Toulouse 31058, France.,

    Carine Mantoulan, Bernadette Roge & Kerstin Wittemeyer

  38. Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, UK.,

    Penny Farrar, Anthony P. Monaco, Alistair Pagnamenta & Kirsty Wing

  39. University Department of Child Psychiatry, Athens University, Medical School, Agia Sophia Children’s Hospital, Athens 115, Greece.,

    Katerina Papanikolaou & John Tsiantis

  40. Department of Medicine, School of Epidemiology and Health Science, University of Manchester, Manchester M13 9PT, UK.,

    Andrew Pickles

  41. Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, North Carolina 27599-3366, USA.,

    Joseph Piven

  42. Social, Genetic and Developmental Psychiatry Centre, Institute Of Psychiatry, London SE5 8AF, UK.,

    Michael L. Rutter

  43. Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19108, USA.,

    Gerard D. Schellenberg

  44. The Hospital for Sick Children and Department of Molecular Genetics, The Centre for Applied Genomics and Program in Genetics and Genome Biology, University of Toronto, Toronto, Ontario M5G 1L7, Canada.,

    Xiao-Qing Liu, Christian R. Marshall, Andrew D. Paterson, Dalila Pinto & Stephen W. Scherer

  45. Department of Pediatrics and Howard Hughes Medical Institute Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.,

    Val Sheffield

  46. Vanderbilt Kennedy Center and Center for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee 37232, USA.,

    Emily L. Crawford, James S. Sutcliffe & Brian L. Yaspan

  47. Child Study Centre, Yale University, New Haven, Connecticut 06510, USA.,

    Fred Volkmar

  48. Department of Psychiatry, Carver College of Medicine, Iowa City, Iowa 52242, USA.,

    Thomas H. Wassink

  49. Department of Biostatistics and Medicine, University of Washington, Seattle, Washington 98195, USA.,

    Ellen M. Wijsman

  50. Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2J3, Canada.,

    Lonnie Zwaigenbaum

  51. Instituto Nacional de Saude Dr Ricardo Jorge Instituto Gulbenkian de Cîencia Lisbon, 1600-560 Portugal.,

    Ines Cabrito, Catarina Correia, Tiago Magalhaes & Astrid M. Vicente

  52. Hospital Pediatrico de Coimbra, Coimbra, 3000-300 Portugal.,

    Guiomar Oliveira

  53. Department of Child and Adolescent Psychiatry, Goteborg University, Goteborg S41345, Sweden.,

    Christopher Gillberg

  54. Department of Psychiatry, INSERM U995, Groupe hospitalier Henri Mondor-Albert Chenevier, AP-HP, Créteil, France.,

    Marion Leboyer

  55. Department of Medicine, University of Washington, Seattle, Washington 98195, USA.,

    Olena Korvatska

  56. Department of Child and Adolescent Neurosciences, Stella Maris Institute, 56018 Calambrone (Pisa), Italy.,

    Agatino Battaglia

  57. Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202, USA.,

    Christopher J. McDougle, John I. Nurnberger Jr & David J. Posey

  58. Department of Biology, University of Bologna, 40126 Bologna, Italy.,

    Elena Maestrini

  59. Autism Speaks, New York, New York 10016, USA ,

    Geraldine Dawson

  60. Department of Neurology and Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.,

    Eric M. Morrow, Eric M. Morrow, Seung-Yun Yoo, Robert Sean Hill, Jennifer N. Partlow, Brenda Barry & Christopher A. Walsh

  61. Department of Child Psychiatry, Istanbul Faculty of Medicine, Istanbul University, 34452 Istanbul, Turkey.,

    Nahit M. Mukaddes

  62. Department of Neurosciences and Pediatrics, King Faisal Specialist Hospital and Research Centre, Jeddah 11211, Kingdom of Saudi Arabia.,

    Soher Balkhy & Generoso Gascon

  63. Clinical Neurosciences & Pediatrics, Brown University School of Medicine, Providence, Rhode Island, USA.,

    Generoso Gascon

  64. Department of Neurology, Combined Military Hospital, Lahore, Pakistan.,

    Asif Hashmi

  65. Kuwait Center for Autism, Kuwait City 73455, Kuwait.,

    Samira Al-Saad

  66. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.,

    Robert M. Joseph

  67. Department of Child Psychiatry and Department of Clinical Genetics, Oulu University Hospital and Oulu University, Oulu FIN-90029, Finland.,

    Irma Moilanen, Hanna Ebeling, Marja-Leena Mattila, Sanna Kuusikko, Katja Jussila & Jaakko Ignatius

  68. Medical Genetic Diagnosis Department, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.,

    Maryam Rostami

  69. Casa de Corazon, Taos, New Mexico 87571, USA.,

    Kara Andresen

  70. Centre de recherche du CHUM, Hôpital Notre-Dame, Montréal, H2L 4M1 Quebec, Canada.,

    Julie Gauthier

  71. Sainte-Justine Hospital Research Center, Universite de Montreal, Montreal, H3T 1C5 Quebec, Canada.,

    Laurent Mottron & Guy Rouleau

  72. Department of Medical Genetics, University of Helsinki, Helsinki, FIN-00014, Finland.,

    Karola Rehnstrom, Lennart von Wendt & Leena Peltonen

  73. Department of Molecular Medicine, National Public Health Institute, Helsinki, FIN-00014, Finland.,

    Karola Rehnstrom, Lennart von Wendt & Leena Peltonen

  74. Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.,

    Leena Peltonen

Authors
  1. Lauren A. Weiss
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  2. Dan E. Arking
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Consortia

The Gene Discovery Project of Johns Hopkins & the Autism Consortium

  • Writing group

    • Mark J. Daly
    •  & Aravinda Chakravarti

  • Johns Hopkins University–NIMH genome scan team

    • Dan E. Arking
    • , Camille W. Brune
    • , Kristen West
    • , Ashley O’Connor
    • , Gina Hilton
    • , Rebecca L. Tomlinson
    • , Andrew B. West
    • , Edwin H. Cook Jr
    •  & Aravinda Chakravarti

  • Autism Consortium–AGRE genome scan team

    • Lauren A. Weiss
    • , Todd Green
    • , Shun-Chiao Chang
    • , Stacey Gabriel
    • , Casey Gates
    • , Ellen M. Hanson
    • , Andrew Kirby
    • , Joshua Korn
    • , Finny Kuruvilla
    • , Steven McCarroll
    • , Eric M. Morrow
    • , Benjamin Neale
    • , Shaun Purcell
    • , Roksana Sasanfar
    • , Carrie Sougnez
    • , Christine Stevens
    • , David Altshuler
    • , James Gusella
    • , Susan L. Santangelo
    • , Pamela Sklar
    • , Rudolph Tanzi
    •  & Mark J. Daly

  • Replication teams: Autism Genome Project Consortium (listed alphabetically)

    • Richard Anney
    • , Anthony J. Bailey
    • , Gillian Baird
    • , Agatino Battaglia
    • , Tom Berney
    • , Catalina Betancur
    • , Sven Bölte
    • , Patrick F. Bolton
    • , Jessica Brian
    • , Susan E. Bryson
    • , Joseph D. Buxbaum
    • , Ines Cabrito
    • , Guiqing Cai
    • , Rita M. Cantor
    • , Edwin H. Cook Jr
    • , Hilary Coon
    • , Judith Conroy
    • , Catarina Correia
    • , Christina Corsello
    • , Emily L. Crawford
    • , Michael L. Cuccaro
    • , Geraldine Dawson
    • , Maretha de Jonge
    • , Bernie Devlin
    • , Eftichia Duketis
    • , Sean Ennis
    • , Annette Estes
    • , Penny Farrar
    • , Eric Fombonne
    • , Christine M. Freitag
    • , Louise Gallagher
    • , Daniel H. Geschwind
    • , John Gilbert
    • , Michael Gill
    • , Christopher Gillberg
    • , Jeremy Goldberg
    • , Andrew Green
    • , Jonathan Green
    • , Stephen J. Guter
    • , Jonathan L. Haines
    • , Joachim F. Hallmayer
    • , Vanessa Hus
    • , Sabine M. Klauck
    • , Olena Korvatska
    • , Janine A. Lamb
    • , Magdalena Laskawiec
    • , Marion Leboyer
    • , Ann Le Couteur
    • , Bennett L. Leventhal
    • , Xiao-Qing Liu
    • , Catherine Lord
    • , Linda J. Lotspeich
    • , Elena Maestrini
    • , Tiago Magalhaes
    • , William Mahoney
    • , Carine Mantoulan
    • , Helen McConachie
    • , Christopher J. McDougle
    • , William M. McMahon
    • , Christian R. Marshall
    • , Judith Miller
    • , Nancy J. Minshew
    • , Anthony P. Monaco
    • , Jeff Munson
    • , John I. Nurnberger Jr
    • , Guiomar Oliveira
    • , Alistair Pagnamenta
    • , Katerina Papanikolaou
    • , Jeremy R. Parr
    • , Andrew D. Paterson
    • , Margaret A. Pericak-Vance
    • , Andrew Pickles
    • , Dalila Pinto
    • , Joseph Piven
    • , David J. Posey
    • , Annemarie Poustka
    • , Fritz Poustka
    • , Regina Regan
    • , Jennifer Reichert
    • , Katy Renshaw
    • , Wendy Roberts
    • , Bernadette Roge
    • , Michael L. Rutter
    • , Jeff Salt
    • , Gerard D. Schellenberg
    • , Stephen W. Scherer
    • , Val Sheffield
    • , James S. Sutcliffe
    • , Peter Szatmari
    • , Katherine Tansey
    • , Ann P. Thompson
    • , John Tsiantis
    • , Herman Van Engeland
    • , Astrid M. Vicente
    • , Veronica J. Vieland
    • , Fred Volkmar
    • , Simon Wallace
    • , Thomas H. Wassink
    • , Ellen M. Wijsman
    • , Kirsty Wing
    • , Kerstin Wittemeyer
    • , Brian L. Yaspan
    •  & Lonnie Zwaigenbaum

  • The Homozygosity Mapping Collaborative for Autism

    • Eric M. Morrow
    • , Seung-Yun Yoo
    • , Robert Sean Hill
    • , Nahit M. Mukaddes
    • , Soher Balkhy
    • , Generoso Gascon
    • , Samira Al-Saad
    • , Asif Hashmi
    • , Janice Ware
    • , Robert M. Joseph
    • , Elaine LeClair
    • , Jennifer N. Partlow
    • , Brenda Barry
    •  & Christopher A. Walsh

  • MGH Oulu study

    • David Pauls
    • , Irma Moilanen
    • , Hanna Ebeling
    • , Marja-Leena Mattila
    • , Sanna Kuusikko
    • , Katja Jussila
    •  & Jaakko Ignatius

  • MGH Iran study

    • Roksana Sasanfar
    • , Ala Tolouei
    • , Majid Ghadami
    • , Maryam Rostami
    • , Azam Hosseinipour
    •  & Maryam Valujerdi

  • MGH EDSP study

    • Susan L. Santangelo
    • , Kara Andresen
    • , Brian Winkloski
    •  & Stephen Haddad

  • Children’s Hospital Boston

    • Lou Kunkel
    • , Zak Kohane
    • , Tram Tran
    • , Sek Won Kong
    • , Stephanie Brewster O’Neil
    • , Ellen M. Hanson
    • , Rachel Hundley
    • , Ingrid Holm
    • , Heather Peters
    • , Elizabeth Baroni
    • , Aislyn Cangialose
    • , Lindsay Jackson
    • , Lisa Albers
    • , Ronald Becker
    • , Carolyn Bridgemohan
    • , Sandra Friedman
    • , Kerim Munir
    • , Ramzi Nazir
    • , Judith Palfrey
    • , Alison Schonwald
    • , Esau Simmons
    •  & Leonard A. Rappaport

  • Montreal

    • Julie Gauthier
    • , Laurent Mottron
    • , Ridha Joober
    • , Eric Fombonne
    •  & Guy Rouleau

  • Finland

    • Karola Rehnstrom
    • , Lennart von Wendt
    •  & Leena Peltonen

Corresponding authors

Correspondence to Mark J. Daly, Aravinda Chakravarti, Aravinda Chakravarti or Mark J. Daly.

Ethics declarations

Competing interests

[Competing Interests: Aravinda Chakravarti is a paid member of the Scientific Advisory Board of Affymetrix, a role that is managed by the Committee on Conflict of Interest of the Johns Hopkins University School of Medicine.]

Additional information

Lists of participants and affiliations appears at the end of the paper.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-4 with Legends, Legends for Supplementary Tables 1-2 and Supplementary Tables 3-6. (PDF 523 kb)

Supplementary Tables

This file contains Supplementary Tables 1 and 2 - see file s1 for Legends. (PDF 2330 kb)

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Weiss, L., Arking, D. & The Gene Discovery Project of Johns Hopkins & the Autism Consortium. A genome-wide linkage and association scan reveals novel loci for autism. Nature 461, 802–808 (2009). https://doi.org/10.1038/nature08490

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  • DOI: https://doi.org/10.1038/nature08490

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