Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

iPSYCH-Broad Consortium; Autism Sequencing Consortium

doi:10.1016/j.cell.2019.12.036

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

iPSYCH-Broad Consortium, Autism Sequencing Consortium

Mailman School of Public Health

Research output: Contribution to journal › Article › peer-review

1227 Citations (Scopus)

Abstract

Large-scale sequencing of patients with autism allows identification of over 100 putative ASD-associated genes, the majority of which are neuronally expressed, and investigation of distinct genetic influences on ASD compared with other neurodevelopmental disorders.

Original language	English
Pages (from-to)	568-584.e23
Journal	Cell
Volume	180
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2019.12.036
Publication status	Published - Feb 6 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Funding

We thank the families who participated in this research, without whose contributions genetic studies would be impossible. This study was supported by the AMED ( JP19dm0107087 to B.A. and N.O.), Autism Science Foundation (to S.J.S., S.L.B., and E.B.R.), NHGRI ( HG008895 to M.J.D. and HG002295 to R.C.), NIMH ( MH111658 and MH057881 to B.D., MH111661 and MH100233-03S1 to J.D.B., R01 MH109900 to K.R., MH115957 to M.E.T., MH111660 to M.J.D., and MH111662 to S.J.S. and M.W.S.), NSF ( GRFP 2017240332 to R.C.), the Seaver Foundation (to J.D.B. and S.D.R.), and the Simons Foundation ( SF402281 to S.J.S., M.W.S., B.D., and K.R. and SF573206 to M.E.T.). Funding for individual cohorts is detailed further in the STAR Methods . We thank Tom Nowakowski (UCSF) for facilitating access to the single-cell gene expression data. We thank the families who participated in this research, without whose contributions genetic studies would be impossible. This study was supported by the AMED (JP19dm0107087 to B.A. and N.O.), Autism Science Foundation (to S.J.S. S.L.B. and E.B.R.), NHGRI (HG008895 to M.J.D. and HG002295 to R.C.), NIMH (MH111658 and MH057881 to B.D. MH111661 and MH100233-03S1 to J.D.B. R01 MH109900 to K.R. MH115957 to M.E.T. MH111660 to M.J.D. and MH111662 to S.J.S. and M.W.S.), NSF (GRFP 2017240332 to R.C.), the Seaver Foundation (to J.D.B. and S.D.R.), and the Simons Foundation (SF402281 to S.J.S. M.W.S. B.D. and K.R. and SF573206 to M.E.T.). Funding for individual cohorts is detailed further in the STAR Methods. We thank Tom Nowakowski (UCSF) for facilitating access to the single-cell gene expression data. Resources, C. Stevens, J.R. S. Gerges, G. Schwartz, R.N. E.E.G. C.D. B.A. M.B. A. Brusco, J.B. A. Carracedo, M.C.Y.C. A.G.C. B.H.Y.C. H.C. M.L.C. A. Curr?, B.D.B. E.D. S.D. C.F. M. Fern?ndez-Prieto, G.B.F. C.M.F. J.J.G. E.G. J. Gonz?lez-Pe?as, D.H. E.H. G.E.H. I.H. D.M.H. C.M.H. I.I. S.J. J.J. A.J. M.K. G.P.K. A.K. I.K. S.L.L. T.L. E.T.L. C.L. W.I.L. D.L. F.L. P. Maciel, P. Magnus, D.S.M. G.M. I.M. J.M. N. Minshew, E.M.M.d.S. D.M. E.M.M. O.M. P.B.M. M.M. P. Muglia, B.N. M.N. N.O. A. Palotie, M. Parellada, M.R.P. M. Pericak-Vance, A. Persico, I.P. K.P. A. Reichenberg, A. Renieri, E.R. E.B.R. S. Sandin, G. Schellenberg, S.W.S. S. Schlitt, R.S. I.M.W.S. P.M.S. M.S. G. Soares, C. Stolenberg, P. Suren, E.S. J.S. P. Szatmari, F.T. K.T. E.T. M.d.P.T. C.A.W. L.A.W. T.W. D.W. E.W. J.A.W. T.W.Y. M.H.C.Y. R.Y. E.Z. E.H.C. J.S.S. A.D.B. M.E.T. S.J.S. M.J.D. and J.D.B.; Investigation, F.K.S. J.A.K. J.W. M.S.B. S.D.R. J.A. M. Peng, R.C. J. Grove, L.K. C. Stevens, J.R. M.S.M. M.A. B.S. X.X. A. Bhaduri, H.B. R.N. R.A. B.H.Y.C. R.D. C.M.F. M. Fromer, S. Guter, X.H. S.J. S.L.L. T.L. Y.L. B.M. N. Maltman, K.P. E.B.R. L.S. T.S. P.M.S. J.S. T.W.Y. C.B. E.H.C. M.E.Z. A.D.B. A.E.C. M.E.T. D.J.C. B.D. S.J.S. K.R. M.J.D. and J.D.B.; Data Curation: F.K.S. J.A.K. S.D.R. J.A. R.C. C. Stevens, M.S.M. B.S. A.G.C. S.D. C.M.F. S. Guter, K.E.S. E.M.W. E.H.C. S.J.S. and J.D.B.; Formal Analysis: F.K.S. J.A.K. J.W. M.S.B. J.A. R.C. J. Grove, L.K. A. Bhaduri, U.N. H.B. J.J.G. X.H. I.I. B.N. C.B. A.E.C. D.J.C. B.D. S.J.S. and K.R.; Visualization, J.A.K. J.W. M.S.B. J.A. R.C. A. Bhaduri, A.E.C. B.D. S.J.S. and K.R.; Writing ? Original Draft, F.K.S. J.A.K. J.W. M.S.B. R.C. J.J.G. M.E.T. D.J.C. B.D. S.J.S. K.R. M.J.D. and J.D.B.; Writing ? Review and Editing, F.K.S. M.S.B. S.D.R. J.A. R.C. J. Grove, A. Bhaduri, S.B. I.I. T.L. B.N. K.P. A. Renieri, C.A.W. D.W. T.W.Y. C.B. E.H.C. J.S.S. A.D.B. M.E.T. D.J.C. B.D. S.J.S. K.R. M.J.D. and J.D.B.; Funding Acquisition, C. Stevens, A. Brusco, C.M.F. D.G. N.O. J.S. C.A.W. J.A.W. M.E.Z. A.D.B. M.W.S. M.E.T. D.J.C. B.D. S.J.S. K.R. M.J.D. and J.D.B.; Project Administration, S.D.R. C. Stevens, J.R. A.G.C. P.M.S. J.S. L.T. C.A.W. C.B. E.H.C. L.G. M.G. J.S.S. A.T. M.E.Z. A.D.B. M.W.S. M.E.T. D.J.C. B.D. S.J.S. K.R. M.J.D. and J.D.B. B.M.N. is a member of the scientific advisory board at Deep Genomics and consults for Biogen, Camp4 Therapeutics Corporation, Takeda Pharmaceutical, and Biogen. During the last 3 years, C.M. Freitag has been consultant to Desitin and Roche and receives royalties for books on ASD, ADHD, and MDD.

Funders	Funder number
Project Administration
Seaver foundation
National Science Foundation	GRFP 2017240332
National Institute of Mental Health	MH111658, MH057881, MH100233-03S1, MH115957, MH111660, R01MH113362, MH111661, R01 MH109900, MH111662
National Human Genome Research Institute	HG002295, HG008895
Simons Foundation	SF402281, SF573206
Biogen
Autism Science Foundation
Japan Agency for Medical Research and Development	JP19dm0107087
Beatrice and Samuel A. Seaver Foundation

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2019.12.036

Cite this

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title = "Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism",

abstract = "Large-scale sequencing of patients with autism allows identification of over 100 putative ASD-associated genes, the majority of which are neuronally expressed, and investigation of distinct genetic influences on ASD compared with other neurodevelopmental disorders.",

author = "{iPSYCH-Broad Consortium} and {Autism Sequencing Consortium} and Satterstrom, {F. Kyle} and Kosmicki, {Jack A.} and Jiebiao Wang and Breen, {Michael S.} and {De Rubeis}, Silvia and An, {Joon Yong} and Minshi Peng and Ryan Collins and Jakob Grove and Lambertus Klei and Christine Stevens and Jennifer Reichert and Mulhern, {Maureen S.} and Mykyta Artomov and Sherif Gerges and Brooke Sheppard and Xinyi Xu and Aparna Bhaduri and Utku Norman and Harrison Brand and Grace Schwartz and Rachel Nguyen and Guerrero, {Elizabeth E.} and Caroline Dias and Branko Aleksic and Richard Anney and Mafalda Barbosa and Somer Bishop and Alfredo Brusco and Jonas Bybjerg-Grauholm and Angel Carracedo and Chan, {Marcus C.Y.} and Chiocchetti, {Andreas G.} and Chung, {Brian H.Y.} and Hilary Coon and Cuccaro, {Michael L.} and Aurora Curr{\'o} and {Dalla Bernardina}, Bernardo and Ryan Doan and Enrico Domenici and Shan Dong and Chiara Fallerini and Montserrat Fern{\'a}ndez-Prieto and Ferrero, {Giovanni Battista} and Freitag, {Christine M.} and Menachem Fromer and Gargus, {J. Jay} and Daniel Geschwind and Iuliana Ionita-Laza and Lipkin, {W. Ian}",

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year = "2020",

month = feb,

day = "6",

doi = "10.1016/j.cell.2019.12.036",

language = "English",

volume = "180",

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AU - Wang, Jiebiao

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AU - Grove, Jakob

AU - Klei, Lambertus

AU - Stevens, Christine

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AU - Mulhern, Maureen S.

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AU - Gerges, Sherif

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AU - Xu, Xinyi

AU - Bhaduri, Aparna

AU - Norman, Utku

AU - Brand, Harrison

AU - Schwartz, Grace

AU - Nguyen, Rachel

AU - Guerrero, Elizabeth E.

AU - Dias, Caroline

AU - Aleksic, Branko

AU - Anney, Richard

AU - Barbosa, Mafalda

AU - Bishop, Somer

AU - Brusco, Alfredo

AU - Bybjerg-Grauholm, Jonas

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AU - Chan, Marcus C.Y.

AU - Chiocchetti, Andreas G.

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AU - Coon, Hilary

AU - Cuccaro, Michael L.

AU - Curró, Aurora

AU - Dalla Bernardina, Bernardo

AU - Doan, Ryan

AU - Domenici, Enrico

AU - Dong, Shan

AU - Fallerini, Chiara

AU - Fernández-Prieto, Montserrat

AU - Ferrero, Giovanni Battista

AU - Freitag, Christine M.

AU - Fromer, Menachem

AU - Gargus, J. Jay

AU - Geschwind, Daniel

AU - Ionita-Laza, Iuliana

AU - Lipkin, W. Ian

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Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

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