@article{46b2f256392c41258113bcab09d3d230,
title = "Common genetic variants on 5p14.1 associate with autism spectrum disorders",
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.",
author = "Kai Wang and Haitao Zhang and Deqiong Ma and Maja Bucan and Glessner, {Joseph T.} and Abrahams, {Brett S.} and Daria Salyakina and Marcin Imielinski and Bradfield, {Jonathan P.} and Sleiman, {Patrick M A} and Kim, {Cecilia E.} and Cuiping Hou and Edward Frackelton and Rosetta Chiavacci and Nagahide Takahashi and Takeshi Sakurai and Eric Rappaport and Lajonchere, {Clara M.} and Jeffrey Munson and Annette Estes and Olena Korvatska and Joseph Piven and Sonnenblick, {Lisa I.} and {Alvarez Retuerto}, {Ana I.} and Herman, {Edward I.} and Hongmei Dong and Ted Hutman and Marian Sigman and Sally Ozonoff and Ami Klin and Thomas Owley and Sweeney, {John A.} and Brune, {Camille W.} and Cantor, {Rita M.} and Raphael Bernier and Gilbert, {John R.} and Cuccaro, {Michael L.} and McMahon, {William M.} and Judith Miller and State, {Matthew W.} and Wassink, {Thomas H.} and Hilary Coon and Levy, {Susan E.} and Schultz, {Robert T.} and Nurnberger, {John I.} and Haines, {Jonathan L.} and Sutcliffe, {James S.} and Cook, {Edwin H.} and Minshew, {Nancy J.} and Buxbaum, {Joseph D.} and Geraldine Dawson and Grant, {Struan F A} and Geschwind, {Daniel H.} and Pericak-Vance, {Margaret A.} and Schellenberg, {Gerard D.} and Hakon Hakonarson",
note = "Funding Information: Acknowledgements We gratefully thank all the children with ASDs and their families at the participating study sites who were enrolled in this study and all the control subjects who donated blood samples to Children{\textquoteright}s Hospital of Philadelphia (CHOP) for genetic research purposes. We also acknowledge the resources provided by the AGRE Consortium (D. H. Geschwind, M. Bucan, W. T. Brown, J. D. Buxbaum, R. M. Cantor, J. N. Constantino, T. C. Gilliam, C. M. Lajonchere, D. H. Ledbetter, C. Lese-Martin, J. Miller, S. F. Nelson, G. D. Schellenberg, C. A. Samango-Sprouse, S. Spence, M. State, R. E. Tanzi) and the participating families. AGRE is a program of Autism Speaks and is at present supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to C. M. Lajonchere (PI), and formerly by grant MH64547 to D. H. Geschwind (PI). We thank the technical staff at the Center for Applied Genomics at CHOP for producing the genotypes used for analyses, and the nursing, medical assistant and medical staff for their help with recruitment of patient and control subjects for the study. We thank R. Liu and I. Lindquist for helping with CNV validation. We thank D. J. Hedges, H. N. Cukier, J. L. McCauley, G. W. Beecham, H. H. Wright, R. K. Abramson, E. R. Martin and J. P. Hussman for their comments, advice and statistical support, and the laboratory core and the autism clinical personnel at the Miami Institute for Human Genomics and the autism clinical staff at the Vanderbilt Center for Human Genetics Research. A subset of the CAP participants was ascertained while M.A.P.-V. was a faculty member at Duke University. We thank the National Institutes of Health (NIH)-funded Developmental Brain and Tissue Bank at University of Maryland for access to the fetal brain tissues used in these studies (National Institute of Child Health and Human Development Contract no. NO1-HD-4-3368 and NO1-HD-4-3383). 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{\textquoteright}s Hospital of Philadelphia. 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). We also acknowledge the partial support to CAP cohort from the Autism Genome Project.",
year = "2009",
month = may,
day = "28",
doi = "10.1038/nature07999",
language = "English (US)",
volume = "459",
pages = "528--533",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7246",
}