Research Article

No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network†

  1. Bernie Devlin1,
  2. Pamela Bennett2,
  3. Edwin H. Cook, Jr.3,
  4. Geraldine Dawson4,
  5. David Gonen3,
  6. Elena L. Grigorenko5,
  7. William McMahon2,
  8. David Pauls6,
  9. Moyra Smith7,
  10. M. Anne Spence7,
  11. Gerard D. Schellenberg8,9,*

Article first published online: 10 JUL 2002

DOI: 10.1002/ajmg.10603

Issue

American Journal of Medical Genetics

American Journal of Medical Genetics

Volume 114, Issue 6, pages 667–672, 8 August 2002

Additional Information

How to Cite

Devlin, B., Bennett, P., Cook,, E. H., Dawson, G., Gonen, D., Grigorenko, E. L., McMahon, W., Pauls, D., Smith, M., Spence, M. A. and Schellenberg, G. D. (2002), No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network. Am. J. Med. Genet., 114: 667–672. doi: 10.1002/ajmg.10603

Author Information

  1. 1

    Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania

  2. 2

    Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Utah, Salt Lake City, Utah

  3. 3

    Child and Adolescent Psychiatry, Department of Psychiatry, Laboratory of Developmental Neuroscience, Department of Obstetrics, University of Chicago, Chicago, Illinois

  4. 4

    Department of Psychology, University of Washington, Seattle, Washington

  5. 5

    Child Study Center and Department of Psychology, Yale University School of Medicine, New Haven, Connecticut

  6. 6

    Unit of Psychiatric and Neurodevelopmental Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

  7. 7

    Department of Pediatrics, University of California, Irvine, Irvine, California

  8. 8

    Veterans Affairs Medical Center, Seattle, Washington

  9. 9

    Departments of Medicine, Neurology and Pharmacology, University of Washington, Seattle, Washington

*Veterans Affairs Medical Center (182b), 1660 S. Columbian Road, Seattle, WA, 98108.

  1. †

    Members of the Collaborative Programs of Excellence in Autism (CPEA) Genetics Network: H. Coon, J. Lainart, University of Utah; S.-J. Kim, B. Leventhal, C. Lord, University of Chicago; J. Escamilla, University of California, Irvine; R. Abbott, A. Estes, J. Munson, P. Rudell, University of Washington.

Publication History

  1. Issue published online: 23 OCT 2002
  2. Article first published online: 10 JUL 2002
  3. Manuscript Accepted: 18 APR 2002
  4. Manuscript Received: 26 NOV 2001

Funded by

  • NICHD/NIDCD. Grant Numbers: PO1HD34565, PO1 HD35476
  • National Institute of Mental Health. Grant Number: MH57881
  • National Center for Research and Resources. Grant Number: M01-RR00064
  • Devonshire Foundation

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Keywords:

  • autism;
  • HOXA1;
  • Asperger syndrome;
  • pervasive developmental disorder;
  • genetic association;
  • autistic disorder

Abstract

A recent study by Ingram et al. [2000b: Teratology 62:393–405] suggests a His73Arg polymorphism (A:G) in HOXA1 contributes substantially to a liability for autism. Using 68 individuals diagnosed with Autism Spectrum Disorders, they found a significant dearth of G homozygotes and biased transmission of G alleles from parents to affected offspring, especially from mothers. Because the connection between HOXA1 and liability to autism is compelling, we attempted to replicate their finding using a larger, independent sample from the Collaborative Programs of Excellence in Autism (CPEA) network. In our data, genotype frequencies conform to Hardy-Weinberg equilibrium; allele transmissions meet Mendelian expectations; and there is no obvious sex-biased allele transmission. Based on our sample size, calculations suggest that we would have at least 95% power to detect linkage and association even if the A:G polymorphism were to account for only 1% of the heritability of autism. Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 His73Arg in liability to autism. © 2002 Wiley-Liss, Inc.

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