Year: 2010
Type: article
Study design: Observational Study
Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddq307
Authors: R. Anney, L. Klei, D. Pinto, R. Regan, J. Conroy, T. R. Magalhaes, C. Correia, B. S. Abrahams, N. Sykes, A. T. Pagnamenta, J. Almeida, E. Bacchelli, A. J. Bailey, G. Baird, A. Battaglia, T. Berney, N. Bolshakova, S. Bolte, P. F. Bolton, T. Bourgeron, S. Brennan, J. Brian, A. R. Carson, G. Casallo, J. Casey, S. H. Chu, L. Cochrane, C. Corsello, E. L. Crawford, A. Crossett, G. Dawson, M. de Jonge, R. Delorme, I. Drmic, E. Duketis, F. Duque, A. Estes, P. Farrar, B. A. Fernandez, S. E. Folstein, E. Fombonne, C. M. Freitag, J. Gilbert, C. Gillberg, J. T. Glessner, J. Goldberg, J. Green, S. J. Guter, H. Hakonarson, E. A. Heron, M. Hill, R. Holt, J. L. Howe, G. Hughes, V. Hus, R. Igliozzi, C. Kim, S. M. Klauck, A. Kolevzon, O. Korvatska, V. Kustanovich, C. M. Lajonchere, J. A. Lamb, M. Laskawiec, M. Leboyer, A. Le Couteur, B. L. Leventhal, A. C. Lionel, X.-Q. Liu, C. Lord, L. Lotspeich, S. C. Lund, E. Maestrini, W. Mahoney, C. Mantoulan, C. R. Marshall, H. McConachie, C. J. McDougle, J. McGrath, W. M. McMahon, N. M. Melhem, A. Merikangas, O. Migita, N. J. Minshew, G. K. Mirza, J. Munson, S. F. Nelson, C. Noakes, A. Noor, G. Nygren, G. Oliveira, K. Papanikolaou, J. R. Parr, B. Parrini, T. Paton, A. Pickles, J. Piven, D. J. Posey, A. Poustka, F. Poustka, A. Prasad, J. Ragoussis, K. Renshaw, J. Rickaby, W. Roberts, K. Roeder, B. Roge, M. L. Rutter, L. J. Bierut, J. P. Rice, J. Salt, K. Sansom, D. Sato, R. Segurado, L. Senman, N. Shah, V. C. Sheffield, L. Soorya, I. Sousa, V. Stoppioni, C. Strawbridge, R. Tancredi, K. Tansey, B. Thiruvahindrapduram, A. P. Thompson, S. Thomson, A. Tryfon, J. Tsiantis, H. Van Engeland, J. B. Vincent, F. Volkmar, S. Wallace, K. Wang, Z. Wang, T. H. Wassink, K. Wing, K. Wittemeyer, S. Wood, B. L. Yaspan, D. Zurawiecki, L. Zwaigenbaum, C. Betancur, J. D. Buxbaum, R. M. Cantor, E. H. Cook, H. Coon, M. L. Cuccaro, L. Gallagher, D. H. Geschwind, M. Gill, J. L. Haines, J. Miller, A. P. Monaco, J. I. Nurnberger, A. D. Paterson, M. A. Pericak-Vance, G. D. Schellenberg, S. W. Scherer, J. S. Sutcliffe, P. Szatmari, A. M. Vicente, V. J. Vieland, E. M. Wijsman, B. Devlin, S. Ennis, J. Hallmayer
Institutions: Trinity College Dublin, University of Pittsburgh, University of Toronto, Hospital for Sick Children, Centre for Applied Genomics, University College Dublin, University of Lisbon, National Institute of Health Dr. Ricardo Jorge, Instituto Gulbenkian de Ciência, University of California, Los Angeles, Centre for Human Genetics, University of Oxford, Unidade Local de Saúde de Coimbra, University of Bologna, Warneford Hospital, Guy's Hospital, Newcastle University, Goethe University Frankfurt, Centre National de la Recherche Scientifique, Institut Pasteur, Gènes, synapses et cognition, Université Paris Diderot, Carnegie Mellon University, University of Michigan, Vanderbilt University, Autism Speaks, University of North Carolina at Chapel Hill, University Medical Center Utrecht, Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, Memorial University of Newfoundland, Children's Hospital of Philadelphia, University of Miami, German Cancer Research Center, University of Illinois Chicago, McGill University, University of Pennsylvania, University of Gothenburg, McMaster University, University of Iowa, University of Manchester, Icahn School of Medicine at Mount Sinai, Inserm, Fondation FondaMental, Hôpital Albert-Chenevier, Nathan Kline Institute for Psychiatric Research, New York University, Stanford Medicine, Stanford University, Université Toulouse - Jean Jaurès, Indiana University Indianapolis, Indiana University School of Medicine, University of Utah, Centre for Addiction and Mental Health, National and Kapodistrian University of Athens, Children's Hospital Agia Sophia, Washington University in St. Louis, Howard Hughes Medical Institute, Yale University, University of Alberta, Université Pierre-et-Marie-Curie, Vanderbilt University Medical Center, Nationwide Children's Hospital, Battelle, Abigail Wexner Research Institute, The Ohio State University, University of Washington
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funders: Howard Hughes Medical Institute, Autism Speaks, GlaxoSmithKline, Johns Hopkins University, Ontario Innovation Trust, Genome Canada, Wellcome Trust, Health Research Board, Ontario Genomics, Hussman Foundation, Fondation FondaMental, Fondation Orange, Ontario Genomics Institute, Sick Kids Foundation, Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale, Koninklijke Nederlandse Akademie van Wetenschappen, Ministero della Salute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, University of Toronto, Fondation de France, Hospital for Sick Children, National Institutes of Health, Canadian Institutes of Health Research, Medical Research Council, Ontario Ministry of Research and Innovation, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Genetic analysis of 15q11-q13 in Autism, ACE: Translational Studies of Insistence on Sameness in Autism, Genetic Linkage Study of Depression and Anxiety Disorders in an Arab Kindred, UW Autism Center of Excellence, Genetic Studies in Neurological Disorders, G2146332128, G2387867334, Study of Addiction: Genetics and Environment, MOLECULAR GENETICS OF AUTISM, G3069078531, Identification and functional analysis of susceptibility genes in multifactorial disease., Greater New York Autism Research Center of Excellence, G4303903696, The Collaborative Genetic Study of Nicotine Dependence, Genome Wide Association Coordinating Center, Case Control Candidate Gene Study of Addiction, Molecular and Genetic Epidemiology of Autism, Genetics Association in Schizophrenia and Other Disorders, Unraveling the Genetic Etiology of Autism, RUPP-PI, G564567861, NEUROBIOLOGY AND GENETICS OF AUTISM, JH/CIDR Genotyping for Genome-Wide Association Studies, Neurobiologic and Cognitive Mechanisms of Autism, G6132732, G6232008589, Genetic association in schizophrenia and other disorders, A Comprehensive Approach to Identification of Autism Susceptibility Genes, FAMILY STUDY OF COCAINE DEPENDENCE, INFRASTRUCTURE TO FACILITATE DISCOVERY OF AUTISM GENES, Heterogeneity in Autism Spectrum Disorders: Biological Mechanisms, Trajectories, and Treatment Response, G7093047072, G7522350138, G7816143599, G8097169153, COLLABORATIVE LINKAGE STUDY OF AUTISM, G88852782, G9000027892, Postdoctoral Program in Functional Neurogenomics, Collaborative Study on the Genetics of Alcoholism (COGA)., G98478226
OpenAlex ID: W2152157708