OCD Collaborative Genetics Association Study

描述（由申请人提供）：OCD合作遗传学小组拟开展一项早发性强迫症（OCD）全基因组关联研究。这个由六个学术中心组成的小组在过去的五年里合作进行了一项正在进行的强迫症遗传联系研究，并证明了招募和诊断患有这种疾病的个体的能力。在这项提案中，合作将对2000名强迫症患者进行精神病学评估，并收集这些患者及其父母的DNA。基因分型和分析将分两个阶段进行。在第一阶段，将在Illumina实验室用55万个单核苷酸多态性（snp）面板对1000个三联体进行基因分型。我们将估计所有55万个snp的遗传效应大小，然后根据它们的条件功率估计对所有snp进行排名。功率排名最高的1534个snp将在第二阶段（1000个三元组）进行基因分型。两个阶段的综合p值（只需要对1534个比较进行调整，但不需要对550,000个比较进行调整）小于5%/1534 （Bonferroni校正）将被认为是全基因组显著性的。提出的间接关联方法将采用更直接的关联技术（基于基因）、创新的基因-基因相互作用分析（基于基因簇）以及其他分子和功能方法。这些分析的结果将指导未来的分子策略，以确定参与强迫症发病机制的基因。来自样本的临床和基因型数据将公开用于强迫症遗传学研究。

DESCRIPTION (provided by applicant): 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.