Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration

Brain Lang. 2017 Nov;174:50-60. doi: 10.1016/j.bandl.2017.07.005. Epub 2017 Jul 22.


Three lines of evidence motivated this study. 1) CNTNAP2 variation is associated with autism risk and speech-language development. 2) CNTNAP2 variations are associated with differences in white matter (WM) tracts comprising the speech-language circuitry. 3) Children with autism show impairment in multisensory speech perception. Here, we asked whether an autism risk-associated CNTNAP2 single nucleotide polymorphism in neurotypical adults was associated with multisensory speech perception performance, and whether such a genotype-phenotype association was mediated through white matter tract integrity in speech-language circuitry. Risk genotype at rs7794745 was associated with decreased benefit from visual speech and lower fractional anisotropy (FA) in several WM tracts (right precentral gyrus, left anterior corona radiata, right retrolenticular internal capsule). These structural connectivity differences were found to mediate the effect of genotype on audiovisual speech perception, shedding light on possible pathogenic pathways in autism and biological sources of inter-individual variation in audiovisual speech processing in neurotypicals.

Keywords: Autism; CNTNAP2; Connectome; Development; Fractional anisotropy; Genetics; Iffusion tensor imaging; Language; Mediation analysis; Multisensory; Speech perception in noise; Tract based spatial statistics.

MeSH terms

  • Acoustic Stimulation
  • Adult
  • Anisotropy
  • Autistic Disorder / genetics*
  • Autistic Disorder / physiopathology*
  • Brain / pathology*
  • Brain / physiopathology*
  • Female
  • Humans
  • Language Development
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Neural Pathways*
  • Photic Stimulation
  • Polymorphism, Single Nucleotide
  • Speech Perception / genetics*
  • Speech*
  • White Matter / pathology
  • White Matter / physiopathology
  • Young Adult


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