title: Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.
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.
authors.affiliation: UCLA Center for Autism Research and Treatment, Semel Institute of Neuroscience, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Maricela
authors.initials: M
authors.lastname: Alarcón
authors.forename: Brett S
authors.initials: BS
authors.lastname: Abrahams
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stone
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Duvall
authors.forename: Julia V
authors.initials: JV
authors.lastname: Perederiy
authors.forename: Jamee M
authors.initials: JM
authors.lastname: Bomar
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
authors.forename: Christa L
authors.initials: CL
authors.lastname: Martin
authors.forename: David H
authors.initials: DH
authors.lastname: Ledbetter
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D001921:Brain / Q000196:embryology; D002648:Child; D002897:Chromosomes, Human, Pair 7; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007804:Language Development; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins