Document Detail

Protocadherin α (PCDHA) as a novel susceptibility gene for autism.
MedLine Citation:
PMID:  23031252     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Synaptic dysfunction has been shown to be involved in the pathogenesis of autism. We hypothesized that the protocadherin α gene cluster (PCDHA), which is involved in synaptic specificity and in serotonergic innervation of the brain, could be a suitable candidate gene for autism.
METHODS: We examined 14 PCDHA single nucleotide polymorphisms (SNPs) for genetic association with autism in DNA samples of 3211 individuals (841 families, including 574 multiplex families) obtained from the Autism Genetic Resource Exchange.
RESULTS: Five SNPs (rs251379, rs1119032, rs17119271, rs155806 and rs17119346) showed significant associations with autism. The strongest association (p < 0.001) was observed for rs1119032 (z score of risk allele G = 3.415) in multiplex families; SNP associations withstand multiple testing correction in multiplex families (p = 0.041). Haplotypes involving rs1119032 showed very strong associations with autism, withstanding multiple testing corrections. In quantitative transmission disequilibrium testing of multiplex fam - ilies, the G allele of rs1119032 showed a significant association (p = 0.033) with scores on the Autism Diagnostic Interview-Revised (ADI-R)_D (early developmental abnormalities). We also found a significant difference in the distribution of ADI-R_A (social interaction) scores between the A/A, A/G and G/G genotypes of rs17119346 (p = 0.002).
LIMITATIONS: Our results should be replicated in an independent population and/or in samples of different racial backgrounds.
CONCLUSION: Our study provides strong genetic evidence of PCDHA as a potential candidate gene for autism.
Ayyappan Anitha; Ismail Thanseem; Kazuhiko Nakamura; Kazuo Yamada; Yoshimi Iwayama; Tomoko Toyota; Yasuhide Iwata; Katsuaki Suzuki; Toshiro Sugiyama; Masatsugu Tsujii; Takeo Yoshikawa; Norio Mori
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of psychiatry & neuroscience : JPN     Volume:  38     ISSN:  1488-2434     ISO Abbreviation:  J Psychiatry Neurosci     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-12-09     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9107859     Medline TA:  J Psychiatry Neurosci     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  192-8     Citation Subset:  IM    
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MeSH Terms
Autistic Disorder / genetics*
Cadherins / genetics*
Cell Adhesion Molecules / genetics
Genetic Predisposition to Disease
Linkage Disequilibrium
Polymorphism, Single Nucleotide / genetics*
Grant Support
Reg. No./Substance:
0/Cadherins; 0/Cell Adhesion Molecules

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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