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.
No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network†
Article first published online: 10 JUL 2002
Copyright © 2002 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 114, Issue 6, pages 667–672, 8 August 2002
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
- Issue published online: 23 OCT 2002
- Article first published online: 10 JUL 2002
- Manuscript Accepted: 18 APR 2002
- Manuscript Received: 26 NOV 2001
- 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
- Asperger syndrome;
- pervasive developmental disorder;
- genetic association;
- autistic disorder
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.