Protocadherin α ( PCDHA ) as a novel susceptibility gene for autism

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...

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Published in:Journal of psychiatry & neuroscience 2013-05, Vol.38 (3), p.192-198
Main Authors: Anitha, Ayyappan, PhD, Thanseem, Ismail, PhD, Nakamura, Kazuhiko, MD, PhD, Yamada, Kazuo, MD, PhD, Iwayama, Yoshimi, MS, Toyota, Tomoko, MD, PhD, Iwata, Yasuhide, MD, PhD, Suzuki, Katsuaki, MD, PhD, Sugiyama, Toshiro, MD, PhD, Tsujii, Masatsugu, MA, Yoshikawa, Takeo, MD, PhD, Mori, Norio, MD, PhD
Format: Article
Language:fre ; eng
Subjects:
Autism
Autistic Disorder - genetics
Biological and medical sciences
Cadherins
Cadherins - genetics
Cell Adhesion Molecules - genetics
Child clinical studies
Developmental disorders
Female
Fundamental and applied biological sciences. Psychology
Genetic aspects
Genetic Predisposition to Disease
Genetic susceptibility
Genotype
Haplotypes
Humans
Infantile autism
Linkage Disequilibrium
Male
Medical Education
Medical sciences
Polymorphism, Single Nucleotide - genetics
Properties
Psychiatry
Psychoanalysis
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Research Papers
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Summary: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 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.
ISSN:1180-4882
1488-2434
DOI:10.1503/jpn.120058