©2012 Klei et al.; licensee BioMed Central Ltd.
Common genetic variants, acting additively, are a major source of risk for autism
1Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
2Program on Neurogenetics, Yale University School of Medicine, New Haven, Connecticut, USA
3Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA
4Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA
5Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
6Department of Psychology, University of Michigan, Ann Arbor, MI, USA
7Neurogenetics 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, California, USA
8Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
9Division of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
10Department of Psychiatry, McGill University, Montreal Children's Hospital, Montreal, QC, H3Z 1P2, Canada
11Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA
12Geisinger Health System, Danville, Pennsylvania, USA
13Center for Autism and the Developing Brain, Weill Cornell Medical College, White Plains, New York, USA
14Yale Center for Genome Analysis, Orange, Connecticut, USA
15Departments of Pediatrics and Human Genetics, The University of Michigan Medical Center, Ann Arbor, Michigan, USA
16Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA
17Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island, USA
18Howard Hughes Medical Institute and Division of Genetics, Children's Hospital Boston, and Neurology and Pediatrics, Harvard Medical School Center for Life Sciences, Boston, Massachusetts, USA
19Department of Molecular Physiology & Biophysics, Center for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee, USA
20Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA
21Department of Statistics, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
Received August 20, 2012; Accepted October 4, 2012.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Research supported by grants from the Simons Foundation and MH057881.
: We are grateful to all of the families participating in the Simons Foundation Autism Research Initiative (SFARI) Simplex Collection (SSC). This work was supported by a grant from the Simons Foundation. We wish to thank the SSC principal investigators A.L. Beaudet, R. Bernier, J. Constantino, E.H. Cook, Jr., E. Fombonne, D. Geschwind, D.E. Grice, A. Klin, D.H. Ledbetter, C. Lord, C.L. Martin, D.M. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M.W. State, W. Stone, J.S. Sutcliffe, C.A. Walsh, and E. Wijsman; the coordinators and staff at the SSC sites; the SFARI staff, in particular M. Benedetti; Prometheus Research; the Yale Center of Genomic Analysis staff, in particular M. Mahajan, S. Umlauf, I. Tikhonova and A. Lopez; T. Brooks-Boone, N. Wright-Davis and M. Wojciechowski for their help in administering the project at Yale; I. Hart for support; and G.D. Fischbach, A. Packer, J. Spiro, M. Benedetti and M. Carlson for their helpful suggestions throughout. Approved researchers can obtain the SSC population data set described in this study by applying at https://base.sfari.org
AGP: We used data from the Autism Genome Project (AGP) Consortium - Whole Genome Association and Copy Number Variation Study of over 1,500 Parent-Offspring Trios - Stage I (dbGaP Study Accession: phs000267.v1.p1). Funding for AGP was provided from National Institutes of Health (HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH57881, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261); The Canadian Institutes for Health Research (CIHR); Assistance Publique - Hôpitaux de Paris, France; Autism Speaks UK; Canada Foundation for Innovation/Ontario Innovation Trust; Grant: Po 255/17-4. Deutsche Forschungsgemeinschaft, Germany; EC Sixth FP AUTISM MOLGEN; Fundação Calouste Gulbenkian, Portugal; Fondation de France; Fondation FondaMental, France; Fondation Orange, France; Fondation pour la Recherche Médicale, France; Fundação para a Ciência e Tecnologia, Portugal; The Hospital for Sick Children Foundation and University of Toronto, Canada; INSERM, France; Institut Pasteur, France; Convention 181 of 19.10.2001. Italian Ministry of Health; John P Hussman Foundation, USA; McLaughlin Centre, Canada; Rubicon 825.06.031. Netherlands Organization for Scientific Research; TMF/DA/5801. Royal Netherlands Academy of Arts and Sciences; Ontario Ministry of Research and Innovation, Canada; Seaver Foundation, USA; Swedish Science Council; The Centre for Applied Genomics, Canada; Utah Autism Foundation, USA; Core award 075491/Z/04. Wellcome Trust, UK. Genotype and phenotype data were obtained from dbGap, as provided by AGP Study Investigators.
: These controls were obtained from Database for Genotypes and Phenotypes (dbGap) at http://www.ncbi.nlm.nih.gov/gap
. Funding support for the “CIDR Visceral Adiposity Study” (Study accession number: phs000169.v1.p1) was provided through the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA. The CIDR Visceral Adiposity Study includes a genome-wide association study funded as part of the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Heath ABC Study Investigators.
NGRC: We also used the NINDS dbGaP database from the CIDR: NGRC Parkinson’s Disease Study (dbGap accession number phs000196.v2.p1). The genetic arm of the study has been funded by NIH since 1998 (R01 NS36960, Haydeh Payami, PI). In 2004, the consortium was formalized as a Michael J Fox Foundation Funded Global Genetic Consortium, and an epidemiologic arm was implemented. Genotype and phenotype data were obtained from dbGap, as provided by NGRC Parkinson’s Disease Study Investigators.
For both the HealthABC and NGRC studies, genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C and HHSN268201100011I.