Genetic Association in Austism Disorder

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DESCRIPTION (provided by applicant): Autism is a highly-heritable neurodevelopmental disorder that presents before the age of three and can lead to life-long disability. In the proposed study, SNPs associated with autism will be identified by performing a genome-wide association study. 200,000 SNPs will be genotyped in 100 affected sib-pairs and 400 unrelated controls. The 200,000 SNP markers that will be used in this screen have been selected because they are uniformly distributed across the genome and have allele frequencies greater than 10% in multiple populations, making them a powerful reagent for whole genome association studies. In Phase I, 25% of the genome will be scanned for autism-associated genes, by genotyping 50,000 of the informative SNPs in the affected and unaffected individuals. This will allow the detection and correction of any population stratification bias that exists, and identification of any autism-associated genes in this portion of the genome. In Phase II, the rest of the genome will be scanned, by genotyping the remaining 150,000 SNPs in the same population of affected and unaffected individuals. This study design will provide sufficient power (-80%) to identify all the major autism susceptibility genes and thus identify risk factor profiles associated with a high risk for autism. The association of these SNPs to autism will then be confirmed by genotyping them in a second, independent population. The identification of autism-associated genetic markers will allow the development of diagnostic tools to identify individuals with high risk of developing autism, and could ultimately lead to therapeutic breakthroughs.