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

Author

Listed:
  • 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
    Neuroscience, and Genetics and Genomic Sciences, 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
    Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19014, 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
    Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19014, USA)

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.

Suggested Citation

  • 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 & Cuip, 2009. "Common genetic variants on 5p14.1 associate with autism spectrum disorders," Nature, Nature, vol. 459(7246), pages 528-533, May.
  • Handle: RePEc:nat:nature:v:459:y:2009:i:7246:d:10.1038_nature07999
    DOI: 10.1038/nature07999
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