Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.

Autor:	Sanders SJ; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: stephan.sanders@ucsf.edu., He X; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA., Willsey AJ; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Ercan-Sencicek AG; Department of Neurosurgery, Program on Neurogenetics, Yale University School of Medicine, New Haven, CT 06520, USA., Samocha KE; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02114, USA., Cicek AE; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Computer Engineering, Bilkent University, Ankara, 0680, Turkey., Murtha MT; Department of Neurosurgery, Program on Neurogenetics, Yale University School of Medicine, New Haven, CT 06520, USA., Bal VH; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Bishop SL; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Dong S; Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China., Goldberg AP; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Jinlu C; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Keaney JF 3rd; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06520, USA., Klei L; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Mandell JD; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Moreno-De-Luca D; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA., Poultney CS; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Robinson EB; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA., Smith L; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Solli-Nowlan T; TheLab, Inc., Los Angeles, CA 90068, USA., Su MY; Program in Biophysics, Harvard University, Boston, MA 02115, USA., Teran NA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA., Walker MF; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Werling DM; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA., Beaudet AL; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, T617, Houston, TX 77030, USA., Cantor RM; Departments of Human Genetics and Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095-7088, USA., Fombonne E; Department of Psychiatry and Institute for Development and disability, Oregon Health & Science University, Portland, OR 97239, USA., Geschwind DH; Neurogenetics Program, Department of Neurology and Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Grice DE; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Lord C; Center for Autism and the Developing Brain, Weill Cornell Medical College, White Plains, NY 10605, USA., Lowe JK; Neurogenetics Program, Department of Neurology and Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Mane SM; Yale Center for Genomic Analysis, Yale University School of Medicine, New Haven, CT 06520, USA., Martin DM; Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA., Morrow EM; Department of Molecular Biology, Cell Biology and Biochemistry and Department of Psychiatry and Human Behavior, Brown University, 70 Ship Street, Box G-E4, Providence, RI 02912, USA., Talkowski ME; Center for Human Genetic Research, Departments of Neurology, Psychiatry, and Pathology, Massachusetts General Hospital, Boston, MA 02114, USA., Sutcliffe JS; Department of Molecular Physiology & Biophysics, 6133 MRB III, Center for Molecular Neuroscience, Vanderbilt University, Nashville, TN 37232, USA., Walsh CA; Howard Hughes Medical Institute and Division of Genetics and Genomics, Children's Hospital Boston, and Neurology and Pediatrics, Harvard Medical School Center for Life Sciences, 3 Blackfan Circle, Boston, MA 02115, USA., Yu TW; Howard Hughes Medical Institute and Division of Genetics and Genomics, Children's Hospital Boston, and Neurology and Pediatrics, Harvard Medical School Center for Life Sciences, 3 Blackfan Circle, Boston, MA 02115, USA., Ledbetter DH; Autism & Developmental Medicine Institute, Geisinger Health System, Danville, PA 17822, USA., Martin CL; Autism & Developmental Medicine Institute, Geisinger Health System, Danville, PA 17822, USA., Cook EH; Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, 1747 W. Roosevelt Road, Room 155, Chicago, IL 60637 USA., Buxbaum JD; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Daly MJ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA., Devlin B; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Roeder K; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213, USA., State MW; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.state@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2015 Sep 23; Vol. 87 (6), pp. 1215-1233.
DOI:	10.1016/j.neuron.2015.09.016
Abstrakt:	Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1). (Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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