Association study of the CNS patterning genes and autism in Han Chinese in Taiwan |
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Authors: | Chien Yi-Ling Wu Yu-Yu Chiu Yen-Nan Liu Shih-Kai Tsai Wen-Che Lin Ping-I Chen Chia-Hsiang Gau Susan Shur-Fen Chien Wei-Hsien |
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Affiliation: | a Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwanb Department of Psychiatry, Chang-Gung Memorial Hospital, Kweishan, Taiwanc Department of Child and Adolescent Psychiatry, Taoyuan Mental Hospital, Department of Health, Executive Yuan, Tao-Yuan, Taiwand Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwane Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwanf Institute of Medical Sciences and Graduate Institute of Human Genetics, Tzu-Chi University, Hualien, Taiwang Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwanh Department of Occupational Therapy, College of Medicine, Fu Jen Catholic University, Taiwan |
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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 ± 4.0 years; 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. |
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Keywords: | ADI-R, Autism Diagnostic Interview-Revised ASD, autism spectrum disorder EN2, engrailed 2 FDR, false discovery rate FOXP2, forkhead box P2 HWE, Hardy-Weinberg equilibrium LD, linkage disequilibrium MALDI-TOF MS, matrix-assisted laser desorption/ionization-time of flight mass spectrometry PCR, polymerase chain reaction SAP, shrimp alkaline phosphatase SHANK3, SH3 and multiple ankyrin repeat domains 3 SNP, single nucleotide polymorphism TDT, Transmission disequilibrium test WNT2, the wingless-type MMTV integration site family, member 2 |
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