Polygenic and developmental profiles of autism differ by age at diagnosis
Abstract
Abstract Although autism has historically been conceptualized as a condition that emerges in early childhood 1,2 , many autistic people are diagnosed later in life 3–5 . It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated ( r g = 0.38, s.e. = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit–hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism.
Article Details
Authors (293)
Xinhe Zhang
Jakob Grove
Yuanjun Gu
Cornelia K. Buus
Lea K. Nielsen
Sharon A. S. Neufeld
Mahmoud Koko
Daniel S. Malawsky
Emma M. Wade
Ellen Verhoef
Anna Gui
Laura Hegemann
Carrie Allison
Alex Tsompanidis
Deep Adhya
Rosemary Holt
Omar Al-Rubaie
Ramin Ali Marandi Ghoddousi
Alexander E. P. Heazell
Jonathan Mill
Alice Franklin
Rosie Bamford
Matthew E. Hurles
Mahmoud Mousa
David H. Rowitch
Kathy K. Niakan
Graham J. Burton
Tereza Cindrova-Davies
Deepak P. Srivastava
Lucia Dutan-Polit
Adam Pavlinek
Laura Sichlinger
Roland Nagy
Madeline A. Lancaster
Jose Gonzalez-Martinez
Tal Biron-Shental
Lidia V. Gabis
Dorothea Floris
Richard Bethlehem
Michael V. Lombardo
Marcin Radecki
Meng-Chuan Lai
Yeshaya David Greenberg
Elizabeth Weir
Florina Uzefovsky
Yumnah T. Khan
Juan Pablo Del Rio
David M. Hougaard
Preben Bo Mortensen
Merete Nordentoft
Thomas Werge
Caroline M. Nievergelt
Adam X. Maihofer
Elizabeth G. Atkinson
Chia-Yen Chen
Karmel W. Choi
Jonathan R. I. Coleman
Nikolaos P. Daskalakis
Laramie E. Duncan
Renato Polimanti
Cindy Aaronson
Ananda B. Amstadter
Soren B. Andersen
Ole A. Andreassen
Paul A. Arbisi
Allison E. Ashley-Koch
S. Bryn Austin
Esmina Avdibegoviç
Dragan Babić
Silviu-Alin Bacanu
Dewleen G. Baker
Anthony Batzler
Jean C. Beckham
Sintia Belangero
Corina Benjet
Carisa Bergner
Linda M. Bierer
Joanna M. Biernacka
Laura J. Bierut
Jonathan I. Bisson
Marco P. Boks
Elizabeth A. Bolger
Amber Brandolino
Gerome Breen
Rodrigo Affonseca Bressan
Richard A. Bryant
Angela C. Bustamante
Jonas Bybjerg-Grauholm
Marie Bækvad-Hansen
Sigrid Børte
Leah Cahn
Joseph R. Calabrese
Jose Miguel Caldas-de-Almeida
Chris Chatzinakos
Sheraz Cheema
Sean A. P. Clouston
Lucia Colodro-Conde
Brandon J. Coombes
Carlos S. Cruz-Fuentes
Anders M. Dale
Shareefa Dalvie
Lea K. Davis
Jürgen Deckert
Douglas L. Delahanty
Michelle F. Dennis
Frank Desarnaud
Christopher P. DiPietro
Seth G. Disner
Anna R. Docherty
Katharina Domschke
Grete Dyb
Alma Džubur Kulenović
Howard J. Edenberg
Alexandra Evans
Chiara Fabbri
Negar Fani
Lindsay A. Farrer
Adriana Feder
Norah C. Feeny
Janine D. Flory
David Forbes
Carol E. Franz
Sandro Galea
Melanie E. Garrett
Bizu Gelaye
Joel Gelernter
Elbert Geuze
Charles F. Gillespie
Slavina B. Goleva
Scott D. Gordon
Aferdita Goçi
Lana Ruvolo Grasser
Camila Guindalini
Magali Haas
Saskia Hagenaars
Michael A. Hauser
Andrew C. Heath
Sian M. J. Hemmings
Victor Hesselbrock
Ian B. Hickie
Kelleigh Hogan
David Michael Hougaard
Hailiang Huang
Laura M. Huckins
Kristian Hveem
Miro Jakovljević
Arash Javanbakht
Gregory D. Jenkins
Jessica Johnson
Ian Jones
Tanja Jovanovic
Karen-Inge Karstoft
Milissa L. Kaufman
James L. Kennedy
Ronald C. Kessler
Alaptagin Khan
Nathan A. Kimbrel
Anthony P. King
Nastassja Koen
Roman Kotov
Henry R. Kranzler
Kristi Krebs
William S. Kremen
Pei-Fen Kuan
Bruce R. Lawford
Lauren A. M. Lebois
Kelli Lehto
Daniel F. Levey
Catrin Lewis
Israel Liberzon
Sarah D. Linnstaedt
Mark W. Logue
Adriana Lori
Yi Lu
Benjamin J. Luft
Michelle K. Lupton
Jurjen J. Luykx
Iouri Makotkine
Jessica L. Maples-Keller
Shelby Marchese
Charles Marmar
Nicholas G. Martin
Gabriela A. Martínez-Levy
Kerrie McAloney
Alexander McFarlane
Katie A. McLaughlin
Samuel A. McLean
Sarah E. Medland
Divya Mehta
Jacquelyn Meyers
Vasiliki Michopoulos
Elizabeth A. Mikita
Lili Milani
William Milberg
Mark W. Miller
Rajendra A. Morey
Charles Phillip Morris
Ole Mors
Mary S. Mufford
Elliot C. Nelson
Sonya B. Norman
Nicole R. Nugent
Meaghan O’Donnell
Holly K. Orcutt
Pedro M. Pan
Matthew S. Panizzon
Gita A. Pathak
Edward S. Peters
Alan L. Peterson
Matthew Peverill
Robert H. Pietrzak
Melissa A. Polusny
Bernice Porjesz
Abigail Powers
Xue-Jun Qin
Andrew Ratanatharathorn
Victoria B. Risbrough
Andrea L. Roberts
Alex O. Rothbaum
Barbara O. Rothbaum
Peter Roy-Byrne
Kenneth J. Ruggiero
Ariane Rung
Heiko Runz
Bart P. F. Rutten
Stacey Saenz de Viteri
Giovanni Abrahão Salum
Laura Sampson
Sixto E. Sanchez
Marcos Santoro
Carina Seah
Soraya Seedat
Julia S. Seng
Andrey Shabalin
Christina M. Sheerin
Derrick Silove
Alicia K. Smith
Jordan W. Smoller
Scott R. Sponheim
Dan J. Stein
Synne Stensland
Jennifer S. Stevens
Jennifer A. Sumner
Martin H. Teicher
Wesley K. Thompson
Arun K. Tiwari
Edward Trapido
Monica Uddin
Robert J. Ursano
Unnur Valdimarsdóttir
Miranda Van Hooff
Eric Vermetten
Christiaan H. Vinkers
Joanne Voisey
Yunpeng Wang
Zhewu Wang
Monika Waszczuk
Heike Weber
Frank R. Wendt
Michelle A. Williams
Douglas E. Williamson
Bendik S. Winsvold
Sherry Winternitz
Christiane Wolf
Erika J. Wolf
Yan Xia
Ying Xiong
Rachel Yehuda
Keith A. Young
Ross McD. Young
Clement C. Zai
Gwyneth C. Zai
Mark Zervas
Hongyu Zhao
Lori A. Zoellner
John-Anker Zwart
Terri deRoon-Cassini
Sanne J. H. van Rooij
Leigh L. van den Heuvel
Murray B. Stein
Kerry J. Ressler
Karestan C. Koenen
Daniel H. Geschwind
Naomi R. Wray
Alexandra Havdahl
Angelica Ronald
Beate St Pourcain
Elise B. Robinson
Thomas Bourgeron
Simon Baron-Cohen
Anders D. Børglum
Hilary C. Martin
Varun Warrier