PT - JOURNAL ARTICLE AU - Ayyappan Anitha AU - Ismail Thanseem AU - Kazuhiko Nakamura AU - Kazuo Yamada AU - Yoshimi Iwayama AU - Tomoko Toyota AU - Yasuhide Iwata AU - Katsuaki Suzuki AU - Toshiro Sugiyama AU - Masatsugu Tsujii AU - Takeo Yoshikawa AU - Norio Mori TI - Protocadherin α (<em>PCDHA</em>) as a novel susceptibility gene for autism AID - 10.1503/jpn.120058 DP - 2013 May 01 TA - Journal of Psychiatry and Neuroscience PG - 192--198 VI - 38 IP - 3 4099 - http://jpn.ca/content/38/3/192.short 4100 - http://jpn.ca/content/38/3/192.full SO - J Psychiatry Neurosci2013 May 01; 38 AB - 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 &lt; 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 families, 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.