Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.
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.
Alarcón
Maricela
M
UCLA Center for Autism Research and Treatment, Semel Institute of Neuroscience, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Abrahams
Brett S
BS
Stone
Jennifer L
JL
Duvall
Jacqueline A
JA
Perederiy
Julia V
JV
Bomar
Jamee M
JM
Sebat
Jonathan
J
Wigler
Michael
M
Martin
Christa L
CL
Ledbetter
David H
DH
Nelson
Stanley F
SF
Cantor
Rita M
RM
Geschwind
Daniel H
DH
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
C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins