Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07

AUTHORS

Daniel J Weiner, Emilie M Wigdor, Stephan Ripke, Raymond K Walters, Jack A Kosmicki, Jakob Grove, Kaitlin E Samocha, Jacqueline I Goldstein, Aysu Okbay, Jonas Bybjerg-Grauholm, Thomas Werge, David M Hougaard, Jacob Taylor, PSYCH-Broad Autism Group, Marie Bækvad-Hansen, Ashley Dumont, Christine Hansen, Thomas F Hansen, Daniel Howrigan, Manuel Mattheisen, Jennifer Moran, Ole Mors, Merete Nordentoft, Bent Nørgaard-Pedersen, Timothy Poterba, Jesper Poulsen, Christine Stevens, Psychiatric Genomics Consortium Autism Group, Verneri Anttila, Peter Holmans, Hailiang Huang, Lambertus Klei, Phil H Lee, Sarah E Medland, Benjamin Neale, Lauren A Weiss, Lonnie Zwaigenbaum, Timothy W Yu, Kerstin Wittemeyer, A Jeremy Willsey, Ellen M Wijsman, Thomas H Wassink, Regina Waltes, Christopher A Walsh, Simon Wallace, Jacob A S Vorstman, Veronica J Vieland, Astrid M Vicente, Herman van Engeland, Kathryn Tsang, Ann P Thompson, Peter Szatmari, Oscar Svantesson, Stacy Steinberg, Kari Stefansson, Hreinn Stefansson, Matthew W State, Latha Soorya, Teimuraz Silagadze, Stephen W Scherer, Gerard D Schellenberg, Sven Sandin, Evald Saemundsen, Guy A Rouleau, Bernadette Rogé, Kathryn Roeder, Wendy Roberts, Jennifer Reichert, Abraham Reichenberg, Karola Rehnström, Regina Regan, Fritz Poustka, Christopher S Poultney, Joseph Piven, Dalila Pinto, Margaret A Pericak-Vance, Milica Pejovic-Milovancevic, Marianne G Pedersen, Carsten B Pedersen, Andrew D Paterson, Jeremy R Parr, Alistair T Pagnamenta, Guiomar Oliveira, John I Nurnberger, Michael T Murtha, Susana Mouga, Eric M Morrow, Daniel Moreno De Luca, Anthony P Monaco, Nancy Minshew, Alison Merikangas, William M McMahon, Susan G McGrew, Igor Martsenkovsky, Donna M Martin, Shrikant M Mane, Pall Magnusson, Tiago Magalhaes, Elena Maestrini, Jennifer K Lowe, Catherine Lord, Pat Levitt, Christa Lese Martin, David H Ledbetter, Marion Leboyer, Ann S Le Couteur, Christine Ladd-Acosta, Alexander Kolevzon, Sabine M Klauck, Suma Jacob, Bozenna Iliadou, Christina M Hultman, Irva Hertz-Picciotto, Robert Hendren, Christine S Hansen, Jonathan L Haines, Stephen J Guter, Dorothy E Grice, Jonathan M Green, Andrew Green, Arthur P Goldberg, Christopher Gillberg, John Gilbert, Louise Gallagher, Christine M Freitag, Eric Fombonne, Susan E Folstein, Bridget Fernandez, M Daniele Fallin, A Gulhan Ercan-Sencicek, Sean Ennis, Frederico Duque, Eftichia Duketis, Richard Delorme, Silvia De Rubeis, Maretha V De Jonge, Geraldine Dawson, Michael L Cuccaro, Catarina T Correia, Judith Conroy, Inês C Conceição, Andreas G Chiocchetti, Patrícia B S Celestino-Soper, Jillian Casey, Rita M Cantor, Cátia Café, Sean Brennan, Thomas Bourgeron, Patrick F Bolton, Sven Bölte, Nadia Bolshakova, Catalina Betancur, Raphael Bernier, Arthur L Beaudet, Agatino Battaglia, Vanessa H Bal, Gillian Baird, Anthony J Bailey, Joel S Bader, Elena Bacchelli, Evdokia Anagnostou, David Amaral, Joana Almeida, Joseph D Buxbaum, Aravinda Chakravarti, Edwin H Cook, Hilary Coon, Daniel H Geschwind, Michael Gill, Hakon Hakonarson, Joachim Hallmayer, Aarno Palotie, Susan Santangelo, James S Sutcliffe, Dan E Arking, David Skuse, Bernie Devlin, Richard Anney, Stephan J Sanders, Somer Bishop, Preben Bo Mortensen, Anders D Børglum, George Davey Smith, Mark J Daly, Elise B Robinson

ABSTRACT

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways. More... »

PAGES

978-985

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    7

    VOLUME

    49

    Author Affiliations

  • Broad Institute
  • Charité
  • Harvard University
  • Aarhus University
  • VU University Amsterdam
  • Statens Serum Institut
  • University of Copenhagen
  • Brigham and Women's Hospital
  • Lundbeck Foundation
  • Aarhus University Hospital
  • Cardiff University
  • University of Pittsburgh
  • QIMR Berghofer Medical Research Institute
  • University of California, San Francisco
  • University of Alberta
  • University of Birmingham
  • University of Washington
  • University of Iowa
  • Goethe University Frankfurt
  • Warneford Hospital
  • University Medical Center Utrecht
  • Nationwide Children's Hospital
  • University of Lisbon
  • McMaster University
  • University of Toronto
  • Karolinska Institutet Innovations (Sweden)
  • deCODE Genetics (Iceland)
  • Rush University Medical Center
  • Tbilisi State Medical University
  • University of Pennsylvania
  • McGill University
  • University of Toulouse
  • Carnegie Mellon University
  • Hospital for Sick Children
  • Icahn School of Medicine at Mount Sinai
  • Wellcome Sanger Institute
  • University College Dublin
  • University of North Carolina System
  • University of Miami
  • University of Belgrade
  • Newcastle University
  • Wellcome Centre for Human Genetics
  • University of Coimbra
  • Indiana University – Purdue University Indianapolis
  • Yale University
  • Brown University
  • Tufts University
  • Trinity College Dublin
  • University of Utah
  • Vanderbilt University
  • University of Michigan–Ann Arbor
  • National University Hospital of Iceland
  • University of Bologna
  • University of California Los Angeles
  • Cornell University
  • University of Southern California
  • Autism & Developmental Medicine Institute
  • Geisinger Health System
  • Assistance Publique -Hopitaux De Paris
  • Johns Hopkins University
  • German Cancer Research Center
  • University of Minnesota
  • University of California, Davis
  • University of Illinois at Chicago
  • University of Manchester
  • University of Gothenburg
  • Oregon Health & Science University
  • Memorial University of Newfoundland
  • Hôpital Robert Debré
  • Duke University
  • Temple Street Children's University Hospital
  • Baylor College of Medicine
  • Hospitais da Universidade de Coimbra
  • Paris Diderot University
  • Centre for Mental Health
  • Stockholm County Council
  • Sorbonne University
  • King's College London
  • University of British Columbia
  • Stanford University
  • Maine Medical Center Research Institute
  • University College London
  • University of Bristol
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3863

    DOI

    http://dx.doi.org/10.1038/ng.3863

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085410382

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28504703


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