Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.
Research paper by
Maricela M Alarcón, Brett S BS Abrahams, Jennifer L JL Stone, Jacqueline A JA Duvall, Julia V JV Perederiy, Jamee M JM Bomar, Jonathan J Sebat, Michael M Wigler, Christa L CL Martin, David H DH Ledbetter, Stanley F SF Nelson, Rita M RM Cantor, Daniel H DH Geschwind
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.