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

Kai Wang, Haitao Zhang, Deqiong Ma, Maja Bucan, Joseph T. Glessner, Brett S. Abrahams, Daria Salyakina, Marcin Imielinski, Jonathan P. Bradfield, Patrick M. A. Sleiman, Cecilia E. Kim, Cuiping Hou, Edward Frackelton, Rosetta Chiavacci, Nagahide Takahashi, Takeshi Sakurai, Eric Rappaport, Clara M. Lajonchere, Jeffrey Munson, Annette Estes, Olena Korvatska, Joseph Piven, Lisa I. Sonnenblick, Ana I. Alvarez Retuerto, Edward I. Herman, Hongmei Dong, Ted Hutman, Marian Sigman, Sally Ozonoff, Ami Klin, Thomas Owley, John A. Sweeney, Camille W. Brune, Rita M. Cantor, Raphael Bernier, John R. Gilbert, Michael L. Cuccaro, William M. McMahon, Judith Miller, Matthew W. State, Thomas H. Wassink, Hilary Coon, Susan E. Levy, Robert T. Schultz, John I. Nurnberger, Jonathan L. Haines, James S. Sutcliffe, Edwin H. Cook, Nancy J. Minshew, Joseph D. Buxbaum, Geraldine Dawson, Struan F. A. Grant, Daniel H. Geschwind, Margaret A. Pericak-Vance, Gerard D. Schellenberg and Hakon Hakonarson ()
Additional contact information
Kai Wang: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Haitao Zhang: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Deqiong Ma: University of Miami, Miami, Florida 33101, USA
Maja Bucan: University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA
Joseph T. Glessner: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Brett S. Abrahams: University of California Los Angeles, Los Angeles, California 90095, USA
Daria Salyakina: University of Miami, Miami, Florida 33101, USA
Marcin Imielinski: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Jonathan P. Bradfield: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Patrick M. A. Sleiman: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Cecilia E. Kim: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Cuiping Hou: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Edward Frackelton: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Rosetta Chiavacci: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Nagahide Takahashi: Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York 10029, USA
Takeshi Sakurai: Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York 10029, USA
Eric Rappaport: Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19014, USA
Clara M. Lajonchere: University of Southern California and Autism Speaks, Los Angeles, California 90089, USA
Jeffrey Munson: University of Washington, Seattle, Washington 98105, USA
Annette Estes: University of Washington, Seattle, Washington 98105, USA
Olena Korvatska: University of Washington, Seattle, Washington 98105, USA
Joseph Piven: University of North Carolina and Carolina Institute for Developmental Disabilities, Chapel Hill, North Carolina 27599, USA
Lisa I. Sonnenblick: University of California Los Angeles, Los Angeles, California 90095, USA
Ana I. Alvarez Retuerto: University of California Los Angeles, Los Angeles, California 90095, USA
Edward I. Herman: University of California Los Angeles, Los Angeles, California 90095, USA
Hongmei Dong: University of California Los Angeles, Los Angeles, California 90095, USA
Ted Hutman: University of California Los Angeles, Los Angeles, California 90095, USA
Marian Sigman: University of California Los Angeles, Los Angeles, California 90095, USA
Sally Ozonoff: University of California Davis, Sacramento, California 95817, USA
Ami Klin: Yale University, New Haven, Connecticut 06520, USA
Thomas Owley: University of Illinois at Chicago, Chicago, Illinois 60608, USA
John A. Sweeney: University of Illinois at Chicago, Chicago, Illinois 60608, USA
Camille W. Brune: University of Illinois at Chicago, Chicago, Illinois 60608, USA
Rita M. Cantor: University of California Los Angeles, Los Angeles, California 90095, USA
Raphael Bernier: University of Washington, Seattle, Washington 98105, USA
John R. Gilbert: University of Miami, Miami, Florida 33101, USA
Michael L. Cuccaro: University of Miami, Miami, Florida 33101, USA
William M. McMahon: University of Utah, Salt Lake City, Utah 84132, USA
Judith Miller: University of Utah, Salt Lake City, Utah 84132, USA
Matthew W. State: Yale University, New Haven, Connecticut 06520, USA
Thomas H. Wassink: University of Iowa, Iowa City, Iowa 84112, USA
Hilary Coon: University of Utah, Salt Lake City, Utah 84132, USA
Susan E. Levy: Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19014, USA
Robert T. Schultz: Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19014, USA
John I. Nurnberger: Institute of Psychiatric Research, Indiana University, Indianapolis, Indiana 46202, USA
Jonathan L. Haines: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee 37232, USA
James S. Sutcliffe: Center for Molecular Neuroscience and Vanderbilt Kennedy Center, Vanderbilt University, Nashville, Tennessee 37232, USA
Edwin H. Cook: University of Illinois at Chicago, Chicago, Illinois 60608, USA
Nancy J. Minshew: University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
Joseph D. Buxbaum: Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York 10029, USA
Geraldine Dawson: University of Washington, Seattle, Washington 98105, USA
Struan F. A. Grant: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA
Daniel H. Geschwind: University of California Los Angeles, Los Angeles, California 90095, USA
Margaret A. Pericak-Vance: University of Miami, Miami, Florida 33101, USA
Gerard D. Schellenberg: University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA
Hakon Hakonarson: Center for Applied Genomics, Children’s Hospital of Philadelphia, Pennsylvania 19104, USA

Nature, 2009, vol. 459, issue 7246, 528-533

Abstract: 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 molecules—revealed 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.

Date: 2009
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DOI: 10.1038/nature07999

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