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: 8806061
• 负责人: Steven Andrew McCarroll
• 金额: $ 326.18万
• 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 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8806061
• 关键词: African; Architecture; Bipolar Disorder; Brain Diseases; California; Chronic; Code; Collaborations; Communities; Complex; DNA; Data; Delusions; Deposition; Development; Diagnosis; Disease; Dissection; Elements; Ensure; Etiology; European; Family; First Degree Relative; Frequencies; Functional RNA; Functional disorder; Future; Genes; Genetic; 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; Testing; Universities; Validation; Variant; analytical tool; base; case control; cohort; data sharing; database of Genotypes and Phenotypes; disorder risk; experience; 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; public health relevance; research study; risk variant; tool; trait

 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（由申请人提供）：由博士领导的研究人员之间的这个合作项目的目标。密歇根大学的 Michael Boehnke、哈佛大学和博德研究所的 Steven McCarroll 以及南加州大学的 Carlos Pato 将利用高通量 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通路，并为以下疾病构建数据资源： 未来对这些和其他精神疾病的遗传学研究。该提案建立在我们小组之间在这些重要疾病方面的积极合作以及更广泛的建立在我们构建基因组变异资源（例如用于整个人类遗传学的千个基因组计划）方面的经验的基础上。我们的研究团队结合了高通量遗传学和基因组学的优势、最大限度地发挥新技术优势的创新计算和统计分析的开发和应用以及大型科学联盟的领导力。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 名表型良好且可重新接触的个体进行全基因组测序（约 30 倍覆盖率）和统计分析，这些个体平均分为精神分裂症病例、双相情感障碍病例和精神正常对照，并由同等数量的欧洲血统 (EA)、非洲血统 (AA) 和拉丁裔组成 个人。我们将在所得序列数据中对精神分裂症病例与对照、双相情感障碍病例与对照以及组合病例与对照进行关联分析，并通过与其他研究人员利用可用的相关序列数据进行合作和荟萃分析。我们还将使用这些序列数据作为参考组的一部分，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，以便基于大量个体进行关联分析。最后，我们将分享数据和方法，以支持对其他精神科表型以及更广泛的科学界的类似研究。这些目标的成功完成将为分子病因学提供新的见解，从而促进精神分裂症和双相情感障碍的预防、治疗和诊断方面的突破。