Cited by 818Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersGenetic Associations and Epidemiology

The DOI matches its Crossref record; 65 of the 67 references it cites were found in a registry or an index.

Linkage, Association, and Gene-Expression Analyses Identify CNTNAP2 as an Autism-Susceptibility Gene

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Abstract

Autism is a genetically complex neurodevelopmental syndrome in which language deficits are a core feature. We describe results from two complimentary approaches used to identify risk variants on chromosome 7 that likely contribute to the etiology of autism. A two-stage association study tested 2758 SNPs across a 10 Mb 7q35 language-related autism QTL in AGRE (Autism Genetic Resource Exchange) trios and found significant association with Contactin Associated Protein-Like 2 (CNTNAP2), a strong a priori candidate. Male-only containing families were identified as primarily responsible for this association signal, consistent with the strong male affection bias in ASD and other language-based disorders. Gene-expression analyses in developing human brain further identified CNTNAP2 as enriched in circuits important for language development. Together, these results provide convergent evidence for involvement of CNTNAP2, a Neurexin family member, in autism, and demonstrate a connection between genetic risk for autism and specific brain structures.

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Metadata

Authors
Alarcón, M., Abrahams, B. S., Stone, J. L., Duvall, J. A., Perederiy, J. V., Bomar, J. M., Sebat, J., Wigler, M., Martin, C. L., Ledbetter, D. H., Nelson, S. F., Cantor, R. M., & Geschwind, D. H.
Affiliations
  • University of California, Los Angeles (US)
  • Cold Spring Harbor Laboratory (US)
  • Emory University (US)
Corresponding author
Geschwind, Daniel H.
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2008-01
Volume
82
Issue
1
Pages
150-159
ISSN
0002-9297 (ISSN-L)
OpenAlex
W2126538155
Cited by
818
References
67
Citations by year
2026: 15 · 2025: 12 · 2024: 19 · 2023: 19 · 2022: 26 · 2021: 35 · 2020: 29 · 2019: 28 · 2018: 28 · 2017: 52 · 2016: 43 · 2015: 53 · 2014: 48 · 2013: 69 · 2012: 82
FWCI
44.76
Type
journal article
Language
en
Open access
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
National Institute of Mental Health (R01MH64547, R01MH064547, R01MH076431)
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
CNTNAP2, autism susceptibility, language development, neurexin, genetic linkage, genetic association, trios, brain gene expression, neurodevelopmental disorders
MeSH terms
Autistic Disorder, Brain, Child, Chromosomes, Human, Pair 7, Female, Humans, Language Development, Male, Membrane Proteins, Nerve Tissue Proteins, Gene Expression, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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