title: Heterogeneous association between engrailed-2 and autism in the CPEA network.
abstract: Autism is a neurodevelopmental disorder characterized by an early onset of abnormal social, communicative, and repetitive behavior. Engrailed-2 (EN2) was identified as an autism candidate gene because its influence on cerebellar development in mice parallels neurodevelopmental abnormalities seen in individuals with autism. Studies investigating association between markers at EN2 (chr7q36), a location associated with language disorders, and autism reveal mixed findings. Two positive reports revealed association with two intronic SNPs. Since the associated SNPs were in high linkage disequilibrium and shared similar minor allele frequencies, we chose to test whether one of the SNPs (rs1861972) was associated with autism in three recruiting sites from the NIH Collaborative Programs of Excellence in Autism (CPEA) network. A recessive model revealed significant association with broad autism spectrum disorder. Site specific analyses indicated differential allele transmission by site, despite similar ethnicity, and parental genotypes, suggesting the SNP may contribute to various risk haplotypes. No significant association with autism was found under an additive model for either a broad (autism spectrum disorder) or a narrow (autistic disorder) diagnostic group. Although our findings were not as robust as the previous studies, they suggest that rs1861972 may influence the risk for autism spectrum disorders. Future studies investigating EN2 should consider how the association of variants in this gene with autism could be influenced by differences in phenotype and possible interactions with genotypes at other autism candidate genes.
authors.affiliation: Department of Psychiatry, Institute for Juvenile Research, University of Illinois-Chicago, Chicago, Illinois, USA.
authors.forename: Camille W
authors.initials: CW
authors.lastname: Brune
authors.forename: Elena
authors.initials: E
authors.lastname: Korvatska
authors.forename: Kristina
authors.initials: K
authors.lastname: Allen-Brady
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dawson
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Annette
authors.initials: A
authors.lastname: Estes
authors.forename: Meghann
authors.initials: M
authors.lastname: Hennelly
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hyman
authors.forename: William M
authors.initials: WM
authors.lastname: McMahon
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Munson
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Rodier
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stodgell
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D005190:Family; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007804:Language Development; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000099266:Engrailed 2 Protein