2/3-Whole Genome Sequencing for Schizophrenia and Bipolar Disorder in the GPC

GPC 中精神分裂症和躁郁症的 2/3 全基因组测序

• 批准号: 9306200
• 负责人: Steven Andrew McCarroll
• 金额: $ 327.95万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9306200
• 关键词: African; Architecture; Bipolar Disorder; Brain Diseases; California; Chronic; Clinical; Code; Collaborations; Communities; Complex; Computer Analysis; Copy Number Polymorphism; DNA; Data; Delusions; Deposition; Development; Diagnosis; Disease; Dissection; Elements; Ensure; Etiology; European; Family health status; First Degree Relative; Frequencies; Functional disorder; Future; Genes; Genetic; Genetic study; Genome; Genomic DNA; Genomics; Genotype; Goals; Hallucinations; Haplotypes; Heritability; High-Throughput DNA Sequencing; Human Genetics; Impaired cognition; Individual; Institutes; Knowledge; Latino; Leadership; Libraries; Life; Manic; Mental Depression; Mental disorders; Meta-Analysis; Methods; Michigan; Molecular; Moods; Nucleotides; Participant; Pathway interactions; Persons; Pharmacotherapy; Phenotype; Prevalence; Prevention; Prevention strategy; Process; Psychiatry; Public Health; Quality Control; Research; Research Personnel; Resources; Risk; Schizophrenia; Statistical Data Interpretation; Testing; Universities; Untranslated RNA; Validation; Variant; analytical tool; base; case control; cohort; data resource; data sharing; database of Genotypes and Phenotypes; disorder risk; ethnic diversity; experience; experimental study; follow-up; genetic resource; genetic variant; genome analysis; genome annotation; genome sequencing; genome wide association study; genome-wide; human disease; improved; innovation; insertion/deletion mutation; insight; lifetime risk; new technology; novel therapeutics; phenotypic data; public health relevance; risk variant; tool; trait; whole genome

 DESCRIPTION (provided by applicant): The goal of this collaborative project among investigators led by Drs. Michael Boehnke at the University of Michigan, Steven McCarroll of Harvard University and the Broad Institute, and Carlos Pato at the University of Southern California, is to use high-throughput DNA sequencing to identify genes and pathways that contribute to the risk for schizophrenia and bipolar disorder, and to construct a data resource for future genetic studies of these and other psychiatric disorders. This proposal builds on active collaborations among our groups on these important disorders and more generally on our experience in building genome variation resources, such as the 1000 Genomes Project, that are used throughout human genetics. Our research team combines strengths in high-throughput genetics and genomics, development and application of innovative computational and statistical analyses that maximize the benefits of new technologies, and leadership of large scientific consortia. In four Specific Aims, we propose whole genome sequencing (at ~30x coverage) and statistical analysis of 10,000 well-phenotyped and re-contactable individuals from the Genomic Psychiatry Cohort (GPC), equally divided among schizophrenia cases, bipolar cases, and psychiatrically normal controls, and comprised of equal numbers of European-Ancestry (EA), African-Ancestry (AA), and Latino individuals. We will carry out association analysis comparing schizophrenia cases to controls, bipolar cases to controls, and the combined cases to controls in the resulting sequence data, and by collaboration and meta-analysis with other investigators with relevant sequence data that become available. We will also use these sequence data as part of a reference panel to impute into tens of thousands of other genomes in the broader Psychiatric GWAS Consortium (PGC) data to allow association analysis based on substantially larger numbers of individuals. Finally, we will share data and methods to support similar studies of other psychiatric phenotypes and more broadly across the scientific community. The successful completion of these aims will provide new insights into molecular etiology that could catalyze breakthroughs in the prevention, treatment, and diagnosis of schizophrenia and bipolar disorder.

 描述(申请人提供)：这项由密歇根大学的Michael Boehnke博士、哈佛大学和布罗德研究所的Steven McCarroll博士以及南加州大学的Carlos Pato领导的研究项目的目标是使用高通量DNA测序来识别导致精神分裂症和双相情感障碍风险的基因和途径，并构建一个数据资源 未来对这些和其他精神疾病的遗传学研究。这项建议建立在我们团队在这些重要疾病上的积极合作基础上，以及更广泛地基于我们在构建基因组变异资源方面的经验，例如在整个人类遗传学中使用的1000基因组计划。我们的研究团队结合了高通量遗传学和基因组学、创新计算和统计分析的开发和应用以最大限度地利用新技术的优势，以及大型科学联盟的领导地位。在四个具体目标中，我们建议对来自基因组精神病学队列(GPC)的10,000名表型良好且可再次接触的个体进行全基因组测序(覆盖范围约30倍)和统计分析，这些个体平均分为精神分裂症病例、躁郁症病例和精神正常对照，并包括同等数量的欧洲血统(EA)、非洲血统(AA)和拉丁裔个体。我们将在结果序列数据中对精神分裂症病例与对照组、双相情感障碍病例与对照组以及合并病例与对照组进行关联分析，并通过与其他研究人员的合作和荟萃分析，利用已有的相关序列数据。我们还将使用这些序列数据作为参考小组的一部分，将其归入更广泛的精神病学GWAS联盟(PGC)数据中的数万个其他基因组，以允许基于更大数量的个体进行关联分析。最后，我们将分享数据和方法，以支持其他精神病学表型的类似研究，并更广泛地支持整个科学界。这些目标的成功完成将为分子病因学提供新的见解，可能催化在精神分裂症和双相情感障碍的预防、治疗和诊断方面取得突破。