title: Association study of the CNS patterning genes and autism in Han Chinese in Taiwan.
abstract: Autism is a complex neurodevelopmental disorder with high heritability. Despite different approaches worldwide to identify susceptibility loci or genes for autism spectrum disorders (ASDs), no consistent result has been reported. CNS patterning genes have been recognized as candidate genes for autism based on neuroimage and neuropathology evidence. This study investigated four candidate genes (WNT2, EN2, SHANK3, and FOXP2) by a tag SNP approach in a family-based association study. The trio samples include 1164 subjects from 393 families, including 393 probands (aged 9.1±4.0years; male, 88.6%) diagnosed with autistic disorder (n=373) or Asperger's disorder (n=20) according to the DSM-IV diagnostic criteria and confirmed by the Chinese ADI-R interview. Three tag SNPs of EN2 (7q36), 6 SNPs of WNT2 (7q31-33), 5 SNPs of SHANK3 (22q13.3), 3 SNPs of FOXP2 (7q31) were genotyped. TDT analysis was done to test the association of each tag SNP and haplotype. There was no association with autism for 17 tag SNPs of WNT2, EN2, SHANK3, and FOXP2 based on SNP analyses. Haplotype analyses did not reveal significant association except for the 6 tag SNPs of WNT2 gene showing a significant association on one haplotype composed of rs2896218 and rs6950765 (G-G) (p=0.0095). Other haplotypes composed of rs2896218 and rs6950765 (G-G) were also significantly associated with autism. The present study indicates that SHANK3 may not be a critical gene for the etiology of ASDs in Han Chinese population. Inconsistent findings in EN2 and FOXP2 in the Han Chinese population need further clarification. A haplotype of WNT2 (rs2896218-rs6950765: G-G) is significantly associated with ASDs in our trios samples, this finding warrants further validation by different sample and confirmation by functional study.
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chien
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Wu
authors.forename: Yen-Nan
authors.initials: YN
authors.lastname: Chiu
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Liu
authors.forename: Wen-Che
authors.initials: WC
authors.lastname: Tsai
authors.forename: Ping-I
authors.initials: PI
authors.lastname: Lin
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Chen
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
authors.forename: Wei-Hsien
authors.initials: WH
authors.lastname: Chien
mesh_terms: D044466:Asian People / Q000235:genetics* / Q000523:psychology; D020817:Asperger Syndrome / Q000235:genetics* / Q000523:psychology; D001321:Autistic Disorder / Q000235:genetics* / Q000523:psychology; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D005838:Genotype; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D051154:Wnt2 Protein / Q000235:genetics*; D000099266:Engrailed 2 Protein
chemical_list: D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051154:Wnt2 Protein; D000099266:Engrailed 2 Protein; C465448:FOXP2 protein, human; C492357:SHANK3 protein, human; C495244:WNT2 protein, human