Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
Creators: name: Arking, Dan E.
name: Devlin, Bernie
name: Nørgaard-Pedersen, Bent
name: Nordentoft, Merete
name: Ercan-Sencicek, A. Gulhan
name: Amaral, David
name: Stefansson, Kari
name: Correia, Catarina T.
name: Cantor, Rita M.
name: Wijsman, Ellen M.
name: Samocha, Kaitlin E.
name: Anttila, Verneri
name: Duketis, Eftichia
name: Taylor, Jacob
name: Rogé, Bernadette
name: Hallmayer, Joachim
name: Børglum, Anders D
name: Hansen, Christine S.
name: Regan, Regina
name: Pedersen, Carsten B.
name: Conceição, Inês C.
name: Geschwind, Daniel H.
name: Bybjerg-Grauholm, Jonas
name: Reichenberg, Abraham
name: Buxbaum, Joseph D.
name: Neale, Benjamin
name: Fallin, M. Daniele
name: Weiner, Daniel J.
name: Ledbetter, David H.
name: Anagnostou, Evdokia
name: Dumont, Ashley
name: Van Engeland, Herman
name: Silagadze, Teimuraz
name: Almeida, Joana
name: Santangelo, Susan
name: Sandin, Sven
name: Hansen, Christine
name: Rehnström, Karola
name: Bader, Joel S.
name: Minshew, Nancy
name: Wittemeyer, Kerstin
name: Haines, Jonathan L.
name: Vorstman, Jacob A. S.
name: Bishop, Somer
name: Stevens, Christine
name: Magalhaes, Tiago
name: Hakonarson, Hakon
name: Guter, Stephen J.
name: Skuse, David
name: Levitt, Pat
name: Poultney, Christopher S.
name: Walters, Raymond K.
name: Mortensen, Preben Bo
name: Magnusson, Pall
name: Grice, Dorothy E.
name: Battaglia, Agatino
name: Willsey, A Jeremy
name: Green, Jonathan M.
name: Svantesson, Oscar
name: Lord, Catherine
name: Piven, Joseph
name: Holmans, Peter
name: Bækvad-Hansen, Marie
name: Hultman, Christina M.
name: Ladd-Acosta, Christine
name: Bourgeron, Thomas
name: DeRubeis, Silvia
name: Sutcliffe, James S.
name: Robinson, Elise B.
name: Nurnberger, John I.
name: Baird, Gillian
name: Sanders, Stephan J
name: Mattheisen, Manuel
name: Rouleau, Guy A.
name: Celestino-Soper, Patrícia B. S.
name: Zwaigenbaum, Lonnie
name: Duque, Frederico
name: Ennis, Sean
name: Klei, Lambertus
name: Gill, Michael
name: McMahon, William M.
name: Wigdor, Emilie M.
name: McGrew, Susan G.
name: Wallace, Simon
name: Roberts, Wendy
name: Casey, Jillian
name: Pejovic-Milovancevic, Milica
name: Iliadou, Bozenna
name: Soorya, Latha
name: Cook, Edwin H.
name: Coon, Hilary
name: Stefansson, Hreinn
name: Cuccaro, Michael L.
name: Paterson, Andrew D.
name: Bölte, Sven
name: Bernier, Raphael
name: Merikangas, Alison
name: LeCouteur, Ann S.
name: Poustka, Fritz
name: Parr, Jeremy R.
name: Yu, Timothy W.
name: Thompson, Ann P.
name: Beaudet, Arthur L.
name: Moran, Jennifer
name: Pagnamenta, Alistair T.
name: Goldstein, Jacqueline I.
name: DeLuca, Daniel Moreno
name: Daly, Mark J
name: Green, Andrew
name: Weiss, Lauren A.
name: Palotie, Aarno
name: Folstein, Susan E.
name: Roeder, Kathryn
name: Smith, George Davey
name: Jacob, Suma
name: Mors, Ole
name: Brennan, Sean
name: Grove, Jakob
name: Pinto, Dalila
name: Bal, Vanessa H.
name: Huang, Hailiang
name: Waltes, Regina
name: Cafe, Cátia
name: Bailey, Anthony J.
name: Delorme, Richard
name: Reichert, Jennifer
name: Leboyer, Marion
name: Walsh, Christopher A.
name: Vicente, Astrid M.
name: Goldberg, Arthur P.
name: Dawson, Geraldine
name: DeJonge, Maretha V.
name: Mouga, Susana
name: Hansen, Thomas F.
name: Chiocchetti, Andreas G.
name: Martin, Christa Lese
name: Scherer, Stephen W.
name: Oliveira, Guiomar
name: Klauck, Sabine M.
name: Bolton, Patrick F.
name: Pedersen, Marianne G.
name: Gilbert, John
name: Betancur, Catalina
name: Okbay, Aysu
name: Fombonne, Eric
name: Bolshakova, Nadia
name: Lowe, Jennifer K.
name: Maestrini, Elena
name: Pericak-Vance, Margaret A.
name: Martsenkovsky, Igor
name: Gallagher, Louise
name: Freitag, Christine M.
name: Werge, Thomas
name: Vieland, Veronica J.
name: State, Matthew W.
name: Kolevzon, Alexander
name: Bacchelli, Elena
name: Poulsen, Jesper
name: Monaco, Anthony P.
name: Anney, Richard
name: Howrigan, Daniel
name: Poterba, Timothy
name: Mane, Shrikant M.
name: Hougaard, David M
name: Medland, Sarah E.
name: Chakravarti, Aravinda
name: Hendren, Robert
name: Conroy, Judith
name: Tsang, Kathryn
name: Gillberg, Christopher
name: Steinberg, Stacy
name: Saemundsen, Evald
name: Fernandez, Bridget
name: Ripke, Stephan
name: Murtha, Michael T.
name: Martin, Donna M.
name: Morrow, Eric M.
name: Kosmicki, Jack A.
name: Schellenberg, Gerard D.
name: Lee, Phil H.
name: Wassink, Thomas H.
name: Szatmari, Peter
name: Hertz-Picciotto, Irva
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASDs and to identify subgroups of ASD cases, including those with strong 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 ASDs, schizophrenia, and greater educational attainment is over transmitted to children with ASDs. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strong 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 ASDs’ genetic influences are additive and suggest they create risk through at least partially distinct etiologic pathways.