TY - JOUR
T1 - Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
AU - iPSYCH-Broad Consortium
AU - Autism Sequencing Consortium
AU - Satterstrom, F. Kyle
AU - Kosmicki, Jack A.
AU - Wang, Jiebiao
AU - Breen, Michael S.
AU - De Rubeis, Silvia
AU - An, Joon Yong
AU - Peng, Minshi
AU - Collins, Ryan
AU - Grove, Jakob
AU - Klei, Lambertus
AU - Stevens, Christine
AU - Reichert, Jennifer
AU - Mulhern, Maureen S.
AU - Artomov, Mykyta
AU - Gerges, Sherif
AU - Sheppard, Brooke
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
AU - Carracedo, Angel
AU - Chan, Marcus C.Y.
AU - Chiocchetti, Andreas G.
AU - Chung, Brian H.Y.
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 - Meiri, Gal
AU - Menashe, Idan
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/2/6
Y1 - 2020/2/6
N2 - 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.
AB - 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.
KW - autism spectrum disorder
KW - cell type
KW - cytoskeleton
KW - excitatory neurons
KW - excitatory-inhibitory balance
KW - exome sequencing
KW - genetics
KW - inhibitory neurons
KW - liability
KW - neurodevelopment
UR - http://www.scopus.com/inward/record.url?scp=85078664833&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2019.12.036
DO - 10.1016/j.cell.2019.12.036
M3 - Article
C2 - 31981491
AN - SCOPUS:85078664833
SN - 0092-8674
VL - 180
SP - 568-584.e23
JO - Cell
JF - Cell
IS - 3
ER -