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: 9107509
• 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 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9107509
• 关键词: African; Architecture; Bipolar Disorder; Brain Diseases; California; Chronic; Code; Collaborations; Communities; Complex; Copy Number Polymorphism; DNA; Data; Delusions; Deposition; Development; Diagnosis; Disease; Dissection; Elements; Ensure; Etiology; European; Family; First Degree Relative; Frequencies; Functional disorder; Future; Genes; Genetic; Genetic study; Genome; Genomic DNA; Genomics; Genotype; Goals; Hallucinations; Haplotypes; Health; 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 sharing; database of Genotypes and Phenotypes; disorder risk; ethnic diversity; 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 therapeutics; research study; 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）：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以及南加州大学的卡洛斯帕托领导的研究人员合作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，并构建数据资源， 未来这些和其他精神疾病的遗传学研究。这项提议建立在我们小组在这些重要疾病方面的积极合作基础上，更广泛地说，建立在我们在构建基因组变异资源方面的经验基础上，例如在整个人类遗传学中使用的1000个基因组计划。我们的研究团队结合了高通量遗传学和基因组学的优势，创新计算和统计分析的开发和应用，最大限度地发挥新技术的优势，以及大型科学财团的领导地位。在四个特定目标中，我们提出了全基因组测序（覆盖率约为30倍）和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联系的个体进行统计分析，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病学正常对照，并由相同数量的欧洲人（EA），非洲人（AA）和拉丁美洲人组成。我们将进行关联分析，比较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在所得序列数据中的差异，并通过与其他研究者合作和荟萃分析获得相关序列数据。我们还将使用这些序列数据作为参考面板的一部分，以在更广泛的精神病GWAS联盟（PGC）数据中输入数万个其他基因组，以允许基于大量个体的关联分析。最后，我们将分享数据和方法，以支持其他精神病表型的类似研究，并在科学界更广泛地开展研究。这些目标的成功实现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。