title: No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network.
abstract: A recent study by Ingram et al. [2000b: Teratology 62:393-405] suggests a (His)73(Arg) 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 (His)73(Arg) in liability to autism.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Pamela
authors.initials: P
authors.lastname: Bennett
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dawson
authors.forename: David
authors.initials: D
authors.lastname: Gonen
authors.forename: Elena L
authors.initials: EL
authors.lastname: Grigorenko
authors.forename: William
authors.initials: W
authors.lastname: McMahon
authors.forename: David
authors.initials: D
authors.lastname: Pauls
authors.forename: Moyra
authors.initials: M
authors.lastname: Smith
authors.forename: M Anne
authors.initials: MA
authors.lastname: Spence
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
mesh_terms: D020817:Asperger Syndrome / Q000453:epidemiology / Q000235:genetics*; D001321:Autistic Disorder / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009679:Nuclear Family; D010641:Phenotype; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*; D000099261:Homeobox A1 Protein
chemical_list: D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein