No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network.
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.
Devlin
Bernie
B
Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
Bennett
Pamela
P
Cook
Edwin H
EH
Dawson
Geraldine
G
Gonen
David
D
Grigorenko
Elena L
EL
McMahon
William
W
Pauls
David
D
Smith
Moyra
M
Spence
M Anne
MA
Schellenberg
Gerard D
GD
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
D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein