The OCD Collaborative Genetics Group proposes to conduct a genome-wide association study of early-onset obsessive-compulsive disorder (OCD). This group of six academic centers has collaborated over the past five years on an on-going genetic linkage study of OCD and has demonstrated ability to recruit and diagnose individuals with this disorder. In this proposal, the Collaboration will conduct psychiatric evaluations on 2,000 individuals with obsessive-compulsive disorder (OCD) and collect DNA from these individuals and both their parents. The genotyping and analyses will be performed in two stages. In the first stage 1,000 triads will be genotyped with a 550,000 single nucleotide polymorphisms (SNPs) panel at the Illumina laboratory. We will estimate the genetic effect sizes for all 550,000 SNPs, and then rank all SNPs based on their conditional power estimates. The 1,534 SNPs with the highest power rankings will be genotyped in the second stage (1,000 triads). The combined p-values from the two stages (which will have to be adjusted for only 1,534 comparisons, but not for 550,000) that are less than 5%/1534 (Bonferroni correction) will be considered genome-wide significant. The indirect association approach proposed will be followed up using more direct association techniques (gene based), innovative gene-gene interaction analyses (gene cluster based), and additional molecular and functional approaches. The results of these analyses will guide future molecular strategies to identify genes involved in the pathogenesis of OCD. The clinical and genotype data from the sample will be publicly available for OCD genetics research.
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