Back to Search Start Over

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

Authors :
Shan Dong
Norio Ozaki
Ryan K. C. Yuen
David J. Cutler
Lauren A. Weiss
Catalina Betancur
Abraham Reichenberg
Hassen-Kiss E
Judith Miller
Brooke Sheppard
Yunin Ludena
Astanand Jugessur
Irva Hertz-Picciotto
Donna M. Werling
Aurora Currò
Isaac N. Pessah
Giovanni Battista Ferrero
Somer L. Bishop
Utku Norman
Nancy J. Minshew
Tarjinder Singh
Bernie Devlin
Michael E. Talkowski
Carla Lintas
Susan L. Santangelo
Miia Kaartinen
Gal Meiri
Camilla Stoltenberg
Stephen Sanders
Sherif Gerges
Michael L. Cuccaro
Ryan N. Doan
Suma Jacob
Matthew W. Mosconi
Lambertus Klei
Michael E. Zwick
Kathryn Roeder
Merete Nordentoft
Lauren M. Schmitt
John A. Sweeney
Elizabeth E. Guerrero
Kaija Puura
Alessandra Renieri
Elaine T. Lim
Maureen Mulhern
Danielle de Paula Moreira
Cicek Ae
Nell Maltman
Aparna Bhaduri
Mara Parellada
Sabine Schlitt
Diego Lopergolo
Gun Peggy Knudsen
Christina M. Hultman
Jesslyn Jamison
Rebecca J. Schmidt
So Lun Lee
Iuliana Ionita-Laza
Peter Szatmari
Gerry Schellenberg
Alfredo Brusco
Christine M. Freitag
Andreas G. Chiocchetti
Javier González-Peñas
Michael S. Breen
Jakob Grove
Ryan L. Collins
Mafalda Barbosa
Emilie M. Wigdor
Elise B. Robinson
Cathy A. Stevens
Gabriela Soares
Benjamin M. Neale
Edwin H. Cook
Jiebiao Wang
David M. Hougaard
Enrico Domenici
Gail E. Herman
Patrícia Maciel
Kaitlin E. Samocha
Preben Bo Mortensen
Stephen W. Scherer
Yu Mhc
Elaine Cristina Zachi
Menachem Fromer
Antonio M. Persico
Anders D. Børglum
Minshi Peng
Megan Smith
Elisabetta Trabetti
Rachel Nguyen
Fátima Lopes
James S. Sutcliffe
Trelles Mdp
Xinyi Xu
Emma Wilkinson
Joseph D. Buxbaum
Audrey Thurm
Chiara Fallerini
Jack A. Kosmicki
Michael Gill
Paige M. Siper
Timothy W. Yu
Grace Schwartz
Thomas Werge
Terho Lehtimäki
Itaru Kushima
Jay Gargus
Dalla Bernardina B
Hilary Coon
Maria Rita Passos-Bueno
Stephen J. Guter
Margaret A. Pericak-Vance
Matthew W. State
Per Magnus
Christopher A. Walsh
Evelise Riberi
Ezra Susser
Xin He
Aarno Palotie
Idan Menashe
Eric M. Morrow
Jonas Bybjerg-Grauholm
Pierandrea Muglia
Pål Surén
De Rubeis S
Angel Carracedo
Sven Sandin
Montse Fernández-Prieto
Lara Tang
Lipkin Wi
Ole Mors
Louise Gallagher
Montenegro M. de Souza E
Brian H.Y. Chung
Anney Rjl
Alexander Kolevzon
Dara S. Manoach
Daniel H. Geschwind
Silva Imw
Caroline Dias
Jeremy Willsey
Jennifer Reichert
Elisa Giorgio
Branko Aleksic
Flora Tassone
Satterstrom Fk
Senthil G
Karoline Teufel
Chan Mcy
Harrison Brand
Danielle Halpern
Behrang Mahjani
Mykyta Artomov
Mark J. Daly
Joon Yong An
Lehner T
Publication Year :
2018
Publisher :
Cold Spring Harbor Laboratory, 2018.

Abstract

SummaryWe present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....47c5cce4b31cbcbcecfde47b6cae448f
Full Text :
https://doi.org/10.1101/484113