The WNT2 gene polymorphism associated with speech delay inherent to autism

Res Dev Disabil. Sep-Oct 2012;33(5):1533-40. doi: 10.1016/j.ridd.2012.03.004. Epub 2012 Apr 21.


Previous evidence suggests that language function is modulated by genetic variants on chromosome 7q31-36. However, it is unclear whether this region harbors loci that contribute to speech delay in autism. We previously reported that the WNT2 gene located on 7q31 was associated with the risk of autism. Additionally, two other genes on 7q31-36, FOXP2 and the EN2 genes are also found to play a role in language impairment. Therefore, we hypothesize that the WNT2 gene, FOXP2 gene, and EN2 gene, may act in concert to influence language development in the same population. A total of 373 individuals diagnosed with autistic disorder were recruited in the current study. We selected 6 tag single nucleotide polymorphisms (SNPs) within the WNT2 gene, 3 tag SNPs in the FOXP2, and 3 tag SNPs in the EN2 genes, to study the effect of these genes on language development. Age of first phrase was treated as a quantitative trait. We used general linear model to assess the association between speech delay and these variants. The results show that rs2896218 in the WNT2 gene was moderately significantly associated with age of first phrase (permutation p = 0.0045). A three-locus haplotype in the WNT2 gene was significantly associated with age of first phrase (permutation p = 2 × 10(-4)). Furthermore, we detected an interaction effect on age of first phrase between a SNP rs2228946 in the WNT2 gene and another SNP rs6460013 in the EN2 gene (p = 0.0012). Therefore, the WNT2 gene may play a suggestive role in language development in autistic disorder. Additionally, the WNT2 gene and EN2 gene may act in concert to influence the language development in autism.

Trial registration: NCT00494754.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Autistic Disorder / genetics*
  • Child
  • Chromosomes, Human, Pair 7 / genetics
  • Forkhead Transcription Factors / genetics
  • Haplotypes
  • Homeodomain Proteins / genetics*
  • Humans
  • Language Development Disorders / genetics*
  • Language Development*
  • Linkage Disequilibrium
  • Nerve Tissue Proteins / genetics*
  • Paternal Age
  • Polymorphism, Single Nucleotide / genetics*
  • Wnt2 Protein / genetics*


  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • WNT2 protein, human
  • Wnt2 Protein
  • engrailed 2 protein

Associated data