Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene by Alarcón Maricela, Abrahams Brett S, Stone Jennifer L, Duvall Jacqueline A, Perederiy Julia V, Bomar Jamee M, Sebat Jonathan, Wigler Michael, Martin Christa L, Ledbetter David H, Nelson Stanley F, Cantor Rita M, Geschwind Daniel H in American journal of human genetics (2008). PubMed


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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