美国西奈山伊坎医学院Joseph D. Buxbaum、博德研究所Mark J. Daly、卡内基梅隆大学Kathryn Roeder、加州大学旧金山分校Stephan J. Sanders等研究人员通过大规模外显子组测序，揭示了自闭症神经生物学中的发育和功能变化。相关论文2020年1月23日在线发表在《细胞》上。

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

Author: F. Kyle Satterstrom, Jack A. Kosmicki, Jiebiao Wang, Michael S. Breen, Silvia De 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 Curró, 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-Peas, 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 Lehtimki, 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 M.S. Montenegro, Danielle Moreira, Eric M. Morrow, Ole Mors, Preben Bo Mortensen, Matthew Mosconi, Pierandrea Muglia, Benjamin M. Neale, Merete Nordentoft, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Margaret Pericak-Vance, Antonio M. Persico

Issue&Volume: January 23, 2020

Abstract: We present the largest exome sequencing study of autism spectrum disorder (ASD) todate (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical frameworkto integrate de novo and case-control rare variation, we identify 102 risk genes at a false discoveryrate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas53 show higher frequencies in individuals ascertained to have ASD; comparing ASD caseswith mutations in these groups reveals phenotypic differences. Expressed early inbrain development, most risk genes have roles in regulation of gene expression orneuronal communication (i.e., mutations effect neurodevelopmental and neurophysiologicalchanges), and 13 fall within loci recurrently hit by copy number variants. In cellsfrom the human cortex, expression of risk genes is enriched in excitatory and inhibitoryneuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalanceunderlying ASD.

DOI: 10.1016/j.cell.2019.12.036

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31398-4