Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Humans Autism Spectrum Disorder / genetics Autistic Disorder Genetic Predisposition to Disease DNA Copy Number Variations / genetics Genomics
autism spectrum disorder copy-number variation neurodevelopmental disorders phenotype measures polygenic risk scores rare variants structural variation whole-genome sequencing

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
10 11 2022
Historique:
received: 05 05 2022
revised: 30 08 2022
accepted: 07 10 2022
entrez: 11 11 2022
pubmed: 12 11 2022
medline: 16 11 2022
Statut: ppublish

Résumé

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Identifiants

DOI: 10.1016/j.cell.2022.10.009 PMID: 36368308
pubmed: 36368308
pii: S0092-8674(22)01324-1
doi: 10.1016/j.cell.2022.10.009
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

4409-4427.e18

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH113715
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests E. Anagnostou has received consultation fees from Roche, Quadrant, and Oron; grant funding from Roche; in-kind supports from AMO Pharma and CRR; editorial honoraria from Wiley; and book royalties from APPI and Springer. She co-holds a patent for the device Anxiety Meter (patent # US20160000365A1). S.W.S. is on the Scientific Advisory Committee of Population Bio and serves as a Highly Cited Academic Advisor for King Abdulaziz University, and intellectual property from aspects of his research held at The Hospital for Sick Children are licensed to Athena Diagnostics and Population Bio. These relationships did not influence data interpretation or presentation during this study but are disclosed for potential future considerations.

Auteurs

Brett Trost (B)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Bhooma Thiruvahindrapuram (B)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Ada J S Chan (AJS)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Worrawat Engchuan (W)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Edward J Higginbotham (EJ)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Jennifer L Howe (JL)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Livia O Loureiro (LO)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Miriam S Reuter (MS)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; CGEn, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Delnaz Roshandel (D)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Joe Whitney (J)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Mehdi Zarrei (M)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Matthew Bookman (M)

Verily Life Sciences, South San Francisco, CA 94080, USA.

Cherith Somerville (C)

Ted Rogers Centre for Heart Research, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Rulan Shaath (R)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Mona Abdi (M)

Department of Human Genetics, Sidra Medicine, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.

Elbay Aliyev (E)

Department of Human Genetics, Sidra Medicine, Doha, Qatar.

Rohan V Patel (RV)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Thomas Nalpathamkalam (T)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Giovanna Pellecchia (G)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Omar Hamdan (O)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Gaganjot Kaur (G)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Zhuozhi Wang (Z)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Jeffrey R MacDonald (JR)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

John Wei (J)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Wilson W L Sung (WWL)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Sylvia Lamoureux (S)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Ny Hoang (N)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Autism Research Unit, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Genetic Counselling, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Thanuja Selvanayagam (T)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Autism Research Unit, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Genetic Counselling, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Nicole Deflaux (N)

Verily Life Sciences, South San Francisco, CA 94080, USA.

Melissa Geng (M)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Siavash Ghaffari (S)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

John Bates (J)

Verily Life Sciences, South San Francisco, CA 94080, USA.

Edwin J Young (EJ)

Genome Diagnostics, Department of Paediatric Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Qiliang Ding (Q)

Ted Rogers Centre for Heart Research, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Carole Shum (C)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Lia D'Abate (L)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Clarrisa A Bradley (CA)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Annabel Rutherford (A)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Vernie Aguda (V)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Beverly Apresto (B)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Nan Chen (N)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Sachin Desai (S)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Xiaoyan Du (X)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Matthew L Y Fong (MLY)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Sanjeev Pullenayegum (S)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Kozue Samler (K)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Ting Wang (T)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Karen Ho (K)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Tara Paton (T)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Sergio L Pereira (SL)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Jo-Anne Herbrick (JA)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Richard F Wintle (RF)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Jonathan Fuerth (J)

DNAstack, Toronto, ON M5H 1T1, Canada.

Juti Noppornpitak (J)

DNAstack, Toronto, ON M5H 1T1, Canada.

Heather Ward (H)

DNAstack, Toronto, ON M5H 1T1, Canada.

Patrick Magee (P)

DNAstack, Toronto, ON M5H 1T1, Canada.

Ayman Al Baz (A)

DNAstack, Toronto, ON M5H 1T1, Canada.

Usanthan Kajendirarajah (U)

DNAstack, Toronto, ON M5H 1T1, Canada.

Sharvari Kapadia (S)

DNAstack, Toronto, ON M5H 1T1, Canada.

Jim Vlasblom (J)

DNAstack, Toronto, ON M5H 1T1, Canada.

Monica Valluri (M)

DNAstack, Toronto, ON M5H 1T1, Canada.

Joseph Green (J)

DNAstack, Toronto, ON M5H 1T1, Canada.

Vicki Seifer (V)

Autism Speaks, Princeton, NJ 08540, USA.

Morgan Quirbach (M)

Autism Speaks, Princeton, NJ 08540, USA.

Olivia Rennie (O)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Elizabeth Kelley (E)

Department of Psychology, Queen's University, Kingston, ON K7L 3N6, Canada; Department of Psychiatry, Queen's University, Kingston, ON K7L 7X3, Canada.

Nina Masjedi (N)

Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90024, USA.

Catherine Lord (C)

Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90024, USA.

Michael J Szego (MJ)

Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, ON M5G 1V7, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada.

Ma'n H Zawati (MH)

Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.

Michael Lang (M)

Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.

Lisa J Strug (LJ)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Statistical Sciences, University of Toronto, Toronto, ON M5S 3G3, Canada.

Christian R Marshall (CR)

Genome Diagnostics, Department of Paediatric Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Gregory Costain (G)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.

Kristina Calli (K)

Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada; BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada.

Alana Iaboni (A)

Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada.

Afiqah Yusuf (A)

Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.

Patricia Ambrozewicz (P)

Autism Research Unit, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Psychology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Louise Gallagher (L)

Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin 2, Ireland; Department of Psychiatry, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Child, Youth and Family Services, The Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada; Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada.

David G Amaral (DG)

MIND Institute, University of California, Davis, Sacramento, CA 95817, USA; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA.

Jessica Brian (J)

Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada.

Mayada Elsabbagh (M)

Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.

Stelios Georgiades (S)

Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8N 3K7, Canada.

Daniel S Messinger (DS)

Department of Psychology, University of Miami, Miami, FL 33124, USA.

Sally Ozonoff (S)

MIND Institute, University of California, Davis, Sacramento, CA 95817, USA; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA.

Jonathan Sebat (J)

Department of Psychiatry and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

Calvin Sjaarda (C)

Department of Psychiatry, Queen's University, Kingston, ON K7L 7X3, Canada; Queen's Genomics Lab at Ongwanada, Queen's University, Kingston, ON K7M 8A6, Canada.

Isabel M Smith (IM)

Department of Pediatrics, Dalhousie University, Halifax, NS B3H 4R2, Canada; IWK Health Centre, Halifax, NS B3K 6R8, Canada.

Peter Szatmari (P)

Department of Psychiatry, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, Toronto, ON M6J 1H4, Canada.

Lonnie Zwaigenbaum (L)

Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada.

Azadeh Kushki (A)

Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.

Thomas W Frazier (TW)

Autism Speaks, Princeton, NJ 08540, USA; Department of Psychology, John Carroll University, Cleveland, OH 44118, USA.

Jacob A S Vorstman (JAS)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada.

Khalid A Fakhro (KA)

Department of Human Genetics, Sidra Medicine, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Department of Genetic Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.

Bridget A Fernandez (BA)

Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA; Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA.

M E Suzanne Lewis (MES)

Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada; BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada.

Rosanna Weksberg (R)

Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.

Marc Fiume (M)

DNAstack, Toronto, ON M5H 1T1, Canada.

Ryan K C Yuen (RKC)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Evdokia Anagnostou (E)

Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada.

Neal Sondheimer (N)

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada.

David Glazer (D)

Verily Life Sciences, South San Francisco, CA 94080, USA.

Dean M Hartley (DM)

Autism Speaks, Princeton, NJ 08540, USA.

Stephen W Scherer (SW)

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; McLaughlin Centre, Toronto, ON M5G 0A4, Canada. Electronic address: stephen.scherer@sickkids.ca.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genomic architecture of autism from...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Genomic architecture of autism from...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Trouble autistique › Genomic architecture of autism from...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genomic architecture of autism from...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Genomic architecture of autism from...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Genomic architecture of autism from...