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

Autor:	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., Thiruvahindrapuram B; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., 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., 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., 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., Howe JL; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., 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., 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., Roshandel D; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Whitney J; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., 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., Bookman M; Verily Life Sciences, South San Francisco, CA 94080, USA., Somerville C; Ted Rogers Centre for Heart Research, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., Shaath R; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Abdi M; Department of Human Genetics, Sidra Medicine, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar., Aliyev E; Department of Human Genetics, Sidra Medicine, Doha, Qatar., Patel RV; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Nalpathamkalam T; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Pellecchia G; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Hamdan O; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Kaur G; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Wang Z; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., MacDonald JR; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Wei J; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Sung WWL; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Lamoureux S; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., 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., 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., Deflaux N; Verily Life Sciences, South San Francisco, CA 94080, USA., 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., 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., Bates J; Verily Life Sciences, South San Francisco, CA 94080, USA., 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., Ding Q; Ted Rogers Centre for Heart Research, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., 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., 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., 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., 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., Aguda V; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Apresto B; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Chen N; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Desai S; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Du X; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Fong MLY; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Pullenayegum S; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Samler K; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Wang T; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Ho K; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Paton T; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Pereira SL; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Herbrick JA; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Wintle RF; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Fuerth J; DNAstack, Toronto, ON M5H 1T1, Canada., Noppornpitak J; DNAstack, Toronto, ON M5H 1T1, Canada., Ward H; DNAstack, Toronto, ON M5H 1T1, Canada., Magee P; DNAstack, Toronto, ON M5H 1T1, Canada., Al Baz A; DNAstack, Toronto, ON M5H 1T1, Canada., Kajendirarajah U; DNAstack, Toronto, ON M5H 1T1, Canada., Kapadia S; DNAstack, Toronto, ON M5H 1T1, Canada., Vlasblom J; DNAstack, Toronto, ON M5H 1T1, Canada., Valluri M; DNAstack, Toronto, ON M5H 1T1, Canada., Green J; DNAstack, Toronto, ON M5H 1T1, Canada., Seifer V; Autism Speaks, Princeton, NJ 08540, USA., Quirbach M; Autism Speaks, Princeton, NJ 08540, USA., Rennie O; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Kelley E; Department of Psychology, Queen's University, Kingston, ON K7L 3N6, Canada; Department of Psychiatry, Queen's University, Kingston, ON K7L 7X3, Canada., Masjedi N; Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90024, USA., Lord C; Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90024, USA., 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., Zawati MH; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada., Lang M; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada., 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., 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., 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., 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., Iaboni A; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada., Yusuf A; Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., 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., 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., 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., Brian J; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada., Elsabbagh M; Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., Georgiades S; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8N 3K7, Canada., Messinger DS; Department of Psychology, University of Miami, Miami, FL 33124, USA., 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., Sebat J; Department of Psychiatry and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA., 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., Smith IM; Department of Pediatrics, Dalhousie University, Halifax, NS B3H 4R2, Canada; IWK Health Centre, Halifax, NS B3K 6R8, Canada., 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., Zwaigenbaum L; Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada., Kushki A; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada., Frazier TW; Autism Speaks, Princeton, NJ 08540, USA; Department of Psychology, John Carroll University, Cleveland, OH 44118, USA., 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., 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., 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., 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., 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., Fiume M; DNAstack, Toronto, ON M5H 1T1, Canada., 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., Anagnostou E; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON M4G 1R8, Canada., 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., Glazer D; Verily Life Sciences, South San Francisco, CA 94080, USA., Hartley DM; Autism Speaks, Princeton, NJ 08540, USA., 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.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2022 Nov 10; Vol. 185 (23), pp. 4409-4427.e18.
DOI:	10.1016/j.cell.2022.10.009
Abstrakt:	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. Competing Interests: 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. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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