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

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

doi:10.1101/484113

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

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

F. Kyle Satterstrom, Jack A Kosmicki, Jiebiao Wang, Michael S Breen, Silvia Rubeis, Joon-Yong An, Minshi Peng, Ryan Collins, Jakob Grove, Lambertus Klei, …

Cold Spring Harbor Laboratory

2018-11-30

DOI: https://doi.org/10.1101/484113

Abstract

Summary We 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.

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Title: Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism
Creators: F. Kyle Satterstrom
Jack A Kosmicki
Jiebiao Wang
Michael S Breen
Silvia Rubeis
Joon-Yong An
Minshi Peng
Ryan Collins
Jakob Grove
Lambertus Klei
Christine Stevens
Jennifer Reichert
Maureen S Mulhern
Mykyta Artomov
Sherif Gerges
Brooke Sheppard
Xinyi Xu
Aparna Bhaduri
Utku Norman
Harrison Brand
Grace Schwartz
Rachel Nguyen
Elizabeth E Guerrero
Caroline Dias
Branko Aleksic
Richard Anney
Mafalda Barbosa
Somer Bishop
Alfredo Brusco
Jonas Bybjerg-Grauholm
Angel Carracedo
Marcus C. Y Chan
Andreas G Chiocchetti
Brian H. Y Chung
Hilary Coon
Michael L Cuccaro
Aurora Currò
Bernardo Dalla Bernardina
Ryan Doan
Enrico Domenici
Shan Dong
Chiara Fallerini
Montserrat Fernández-Prieto
Giovanni Battista Ferrero
Christine M Freitag
Menachem Fromer
J. Jay Gargus
Daniel Geschwind
Elisa Giorgio
Javier González-Peñas
Stephen Guter
Danielle Halpern
Emily Hansen-Kiss
Xin He
Gail E Herman
Irva Hertz-Picciotto
David M Hougaard
Christina M Hultman
Iuliana Ionita-Laza
Suma Jacob
Jesslyn Jamison
Astanand Jugessur
Miia Kaartinen
Gun Peggy Knudsen
Alexander Kolevzon
Itaru Kushima
So Lun Lee
Terho Lehtimäki
Elaine T Lim
Carla Lintas
W. Ian Lipkin
Diego Lopergolo
Fátima Lopes
Yunin Ludena
Patricia Maciel
Per Magnus
Behrang Mahjani
Nell Maltman
Dara S Manoach
Gal Meiri
Idan Menashe
Judith Miller
Nancy Minshew
Eduarda Montenegro M Souza
Danielle Moreira
Eric M Morrow
Ole Mors
Preben Bo Mortensen
Matthew Mosconi
Pierandrea Muglia
Benjamin Neale
Merete Nordentoft
Norio Ozaki
Aarno Palotie
Mara Parellada
Maria Rita Passos-Bueno
Margaret Pericak-Vance
Antonio Persico
Isaac Pessah
Kaija Puura
Abraham Reichenberg
Alessandra Renieri
Evelise Riberi
Elise B Robinson
Kaitlin E Samocha
Sven Sandin
Susan L Santangelo
Gerry Schellenberg
Stephen W Scherer
Sabine Schlitt
Rebecca Schmidt
Lauren Schmitt
Isabela Maya W Silva
Tarjinder Singh
Paige M Siper
Moyra Smith
Gabriela Soares
Camilla Stoltenberg
Pål Suren
Ezra Susser
John Sweeney
Peter Szatmari
Lara Tang
Flora Tassone
Karoline Teufel
Elisabetta Trabetti
Maria Del Pilar Trelles
Christopher Walsh
Lauren A Weiss
Thomas Werge
Donna Werling
Emilie M Wigdor
Emma Wilkinson
Jeremy A Willsey
Tim Yu
Mullin H. C Yu
Ryan Yuen
Elaine Zachi
Catalina Betancur
Edwin H Cook
Louise Gallagher
Michael Gill
James S Sutcliffe
Audrey Thurm
Michael E Zwick
Anders D Børglum
Matthew W State
A. Ercument Cicek
Michael E Talkowski
David J Cutler
Bernie Devlin
Stephan J Sanders
Kathryn Roeder
Mark J Daly
Joseph D Buxbaum
Publisher: Cold Spring Harbor Laboratory
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Other
Record Identifier: 991031600155402976