The WNT2 gene polymorphism associated with speech delay inherent to autism
Journal
Research in Developmental Disabilities
Journal Volume
33
Journal Volume
33
Journal Issue
5
Journal Issue
5
Pages
1533-1540
Start Page
1533
End Page
1540
ISSN
1873-3379
Date Issued
2012-09
Author(s)
PING-I LIN
YU-YU WU
CHIA-HSIANG CHEN
YU-SHU HAUNG
SHIH-KAI LIU
Abstract
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. ? 2012 Elsevier Ltd.
SDGs
Other Subjects
transcription factor FOXP2; Wnt2 protein; age; article; autism; child; disease association; DNA polymorphism; EN2 gene; female; FOXP2 gene; gene; gene function; gene interaction; gene locus; genetic association; genetic variability; haplotype; human; language ability; language disability; major clinical study; male; quantitative trait; school child; single nucleotide polymorphism; speech development; statistical model; WNT2 gene; Adolescent; Age of Onset; Autistic Disorder; Child; Chromosomes, Human, Pair 7; Forkhead Transcription Factors; Haplotypes; Homeodomain Proteins; Humans; Language Development; Language Development Disorders; Linkage Disequilibrium; Nerve Tissue Proteins; Paternal Age; Polymorphism, Single Nucleotide; Wnt2 Protein
Type
journal article