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

Am J Hum Genet. 2008 Jan;82(1):150-9. doi: 10.1016/j.ajhg.2007.09.005.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / genetics*
  • Brain / embryology
  • Child
  • Chromosomes, Human, Pair 7
  • Female
  • Gene Expression
  • Genetic Predisposition to Disease*
  • Humans
  • Language Development
  • Male
  • Membrane Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide

Substances

  • CNTNAP2 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins