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

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 Hougaard Jacob Taylor Marie Bækvad-Hansen Ashley Dumont Christine Hansen Thomas Hansen Daniel H Howrigan Manuel Mattheisen Jennifer Moran Ole Mors Merete Nordentoft Bent Pedersen Timothy Poterba Jesper Poulsen Christine S Stevens 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 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 Robert Roberts Jennifer Reichert Abraham Reichenberg Karola Rehnström Regina Regan Fritz Poustka Christopher Poultney Joseph Piven Dalila Pinto Margaret A Pericak-Vance Milica Pejovic-Milovancevic Marianne G Pedersen Carsten B Pedersen Andrew Paterson Jeremy R Parr Alistair T Pagnamenta Guiomar Oliveira John I Nurnberger Michael T Murtha Susan 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 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 1 Bernie 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.
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Nature Genetics, Nature Publishing Group, 2017, pp.978-985. 〈10.1038/ng.3863〉
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Soumis le : vendredi 23 juin 2017 - 14:52:50
Dernière modification le : jeudi 11 janvier 2018 - 06:28:16

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Daniel J Weiner, Emilie M Wigdor, Stephan Ripke, Raymond K Walters, Jack A Kosmicki, et al.. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nature Genetics, Nature Publishing Group, 2017, pp.978-985. 〈10.1038/ng.3863〉. 〈hal-01546155〉

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