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. Published 2007 Wiley‐Liss, Inc.
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Genetic mutations identified in small numbers of people with autism have been generated in mice.
“To incorporate construct validity for the various genetic mutations identified in small numbers of people with autism (12–21), these mutations have been generated in mice (22, 23).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [15]
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- Authors
- Brune, C. W., Korvatska, E., Allen‐Brady, K., Cook, E. H., Dawson, G., Devlin, B., Estes, A., Hennelly, M., Hyman, S. L., McMahon, W. M., Munson, J., Rodier, P. M., Schellenberg, G. D., Stodgell, C. J., & Coon, H.
- Affiliations
- University of Illinois Chicago (US)
- University of Utah (US)
- University of Pittsburgh (US)
- University of Washington (US)
- University of Chicago (US)
- University of Rochester Medicine (US)
- Corresponding author
- Coon, Hilary
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2007-10-19
- Volume
- 147B
- Issue
- 2
- Pages
- 187-193
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2011911237
- Cited by
- 40
- References
- 56
- Citations by year
- 2022: 3 · 2021: 3 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH069359)
- National Center for Research Resources (M01-RR 00064, M01RR000064)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U19HD035466, U19HD35466, U19HD035476, U191HD34565)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- autism spectrum disorder, Engrailed-2, EN2, single nucleotide polymorphisms, genetic association, autistic disorder, cerebellar development, candidate genes, recessive model, allele transmission, risk haplotype
- MeSH terms
- Engrailed 2 Protein, Autistic Disorder, Family, Genotype, Humans, Language Development, Nerve Tissue Proteins, Pedigree, Phenotype, Linkage Disequilibrium, Homeodomain Proteins, Genetic Heterogeneity, Genetic Predisposition to Disease
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