Common genetic variants on 5p14.1 associate with autism spectrum disorders

• Type of Material: Article
• Authors: Kai Wang, Children's Hospital of Philadelphia; Haitao Zhang, Children's Hospital of Philadelphia; Deqiong Ma, University of Miami; Maja Bucan, University of Pennsylvania; Joseph T. Glessner, Children's Hospital of Philadelphia; Brett S. Abrahams, University of California, Los Angeles; Daria Salyakina, University of Miami; Marcin Imielinski, Children's Hospital of Philadelphia; Jonathan P. Bradfield, Children's Hospital of Philadelphia; Patrick M.A. Sleiman, Children's Hospital of Philadelphia; Cecilia E. Kim, Children's Hospital of Philadelphia; Cuiping Hou, Children's Hospital of Philadelphia; Edward Frackelton, Children's Hospital of Philadelphia; Rosetta Chiavacci, Children's Hospital of Philadelphia; Nagahide Takahashi, Mount Sinai School of Medicin; Takeshi Sakurai, Mount Sinai School of Medicin; Eric Rappaport, Children's Hospital of Philadelphia; Clara M. Lajonchere, University of Southern California; Jeffrey Munson, University of Washington; Ami Klin, Emory University
• Language: English
• Date: 2009-05-28
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Macmillan Publishers Limited. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/nature07999
• Title of Journal or Parent Work: Nature
• ISSN: 0028-0836
• Volume: 459
• Issue: 7246
• Start Page: 528
• End Page: 533
• Grant/Funding Information: The study was supported in part by a Research Award from the Margaret Q. Landenberger Foundation (H.H.); a Research Development Award from the Cotswold Foundation (H.H. and S.F.A.G); UL1-RR024134-03 (H.H.); an Alavi-Dabiri fellowship from Mental Retardation and Developmental Disability Research Center at CHOP (K.W.); the Beatrice and Stanley A. Seaver Foundation (J.D.B.); the Department of Veterans Affairs (G.D.S.); NIH grants HD055782-01 (J.Munson, A.E., O.K., G.D. and G.D.S.); MH0666730 (J.D.B.); MH061009 and NS049261 (J.S.S.); HD055751 (E.H.C.); MH69359, M01-RR00064 and the Utah Autism Foundation (H.C., J.Miller and W.M.M.); MH64547, MH081754 (D.H.G.); HD055784 (D.H.G. and M.S.); NS26630, NS36768, MH080647 and a gift from the Hussman Foundation (M.A.P.-V.); the Autism Genome Project Consortium (B.S.A., J.P., C.W.B., D.H.G., T.H.W., W.M.M., H.C., J.I.N., J.S.S., E.H.C., J.Munson, A.E., O.K., J.D.B., B.D. and G.D.S.) funded by Autism Speaks; the Medical Research Council (UK) and the Health Research Board (Ireland).; All genotyping of the AGRE and ACC cohort was supported by an Institutional Development Award to the Center for Applied Genomics (H.H.) at the Children's Hospital of Philadelphia.
• Keywords: GENOME-WIDE ASSOCIATION; Science & Technology; EXPRESSION; Science & Technology - Other Topics; IDENTIFICATION; CHROMOSOME; Multidisciplinary Sciences; DISCONNECTION; UNDERCONNECTIVITY; LOCI; FAMILIAL RISK; LINKAGE; BIPOLAR DISORDER
• Research Categories: Biology, Genetics; Health Sciences, Mental Health

Abstract

Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)two genes encoding neuronal cell-adhesion moleculesrevealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 × 10-8, odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 × 10-8 to 2.1 × 10-10. Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.