Analysis of Whole Genome Association Data for Bipolar Disorder

描述（由申请人提供）：双相情感障碍或躁狂抑郁症是影响世界1%人口的主要精神疾病。它的特点是在躁狂和抑郁两种极端情绪状态之间交替。精神病可能发生在任何一种状态，终生自杀率为17%。我们的11个站点联盟已经资助了超过15年，从双相情感障碍患者及其家庭中收集DMA样本进行遗传研究。我们最近被GAIN选为全基因组关联研究的六种基因分型疾病之一。GAIN将赞助对1158名白种人和400名非裔美国人I型双相情感障碍患者进行基因分型。对照将与相应的精神分裂症项目共享（主要研究者：P. Gejman）。这些样品将由Broad研究所根据GAIN的合同使用Affymetrix 500Kb芯片进行基因分型。这将提供大约50万个snp的基因型和全基因组拷贝数变异的数据。分析将由6个合作站点在合作的基础上进行，每个站点都参与了样本收集。加州大学圣地亚哥分校将作为牵头站点，负责协调参与站点之间的分析工作。将检查病例对照样本的总体子结构，并将此信息用作关联分析中的协变量。将采用单SNP和单倍型两种方法进行关联分析。基因与基因之间的相互作用也将被研究。几种可能的基因上不同的疾病亚型也将分别进行检查。将从全基因组关联中选择相关基因和区域在第二个独立样本中进行复制，该样本包括1000名白种人病例和1000名对照，200名非裔美国人病例和200名对照。复制的基因将受到途径分析，以试图确定参与疾病机制的途径。为了协调各站点之间的分析工作，为所有站点提供数据库、生物信息学和统计支持，并对数据进行初步分析，要求对加州大学圣地亚哥分校站点提供支持。

DESCRIPTION (provided by applicant): Bipolar disorder or manic-depressive illness is a major psychiatric illness that affects 1% of the world's population. It is characterized by alternation between the two extreme mood states of mania and depression. Psychosis can occur in either state and the lifetime suicide rate is 17%. Our 11 site consortium has been funded for over 15 years to collect DMA samples from patients with bipolar disorder and their families for genetic studies. We were recently selected by GAIN to be one of six diseases to be genotyped for whole genome association studies. GAIN will sponsor genotyping of 1158 Caucasian and 400 African American bipolar I cases. Controls will be shared with a corresponding project on schizophrenia (principal investigator: P. Gejman). These samples will be genotyped by the Broad Institute under contract from GAIN using the Affymetrix 500Kb chip. This will provide genotypes on approximately 500,000 SNPs and data on copy number variation genome-wide. The analyses will be conducted on a collaborative basis by 6 collaborating sites each of whom participated in the sample collection. UCSD will serve as the lead site and will be responsible for coordinating the analytic work between the participating sites. The case-control samples will be examined for population substructure and this information will be used as a covariate in the association analysis. Both single SNP and haplotype based methods will be employed for analysis of association. Gene-gene interactions will also be examined. Several possible genetically distinct subforms of illness will also be examined separately. Relevant genes and regions from the genome-wide association will be selected for replication in a second independent sample of 1,000 Caucasian cases and 1,000 controls, and 200 African-American cases and 200 controls. Replicated genes will be subjected to pathway analysis in an attempt to identify pathways involved in mechanisms of disease. Support is requested for the UCSD site in order to coordinate analytic effort between the sites, provide database, bioinformatic and statistical support for all the sites and to conduct the primary analysis of the data.