title: Protocadherin α (PCDHA) as a novel susceptibility gene for autism.
abstract: 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).
  
  
  CONCLUSIONS
  Our results should be replicated in an independent population and/or in samples of different racial backgrounds.
  
  
  CONCLUSIONS
  Our study provides strong genetic evidence of PCDHA as a potential candidate gene for autism.
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules