African Ancestry Genomic Psychiatry Cohort

非洲血统基因组精神病学队列

• 批准号: 10427659
• 负责人: Tim Bernard Bigdeli
• 金额: $ 175.15万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427659
• 关键词: Africa; African; Agreement; Benchmarking; Bipolar Disorder; Bipolar II; Data; Data Set; Diagnosis; Disease; Enrollment; European; Event; Funding; Genetic; Genetic Polymorphism; Genetic Recombination; Genetic Risk; Genome; Genomics; Goals; Haplotypes; Human; Human Genetics; Individual; Institutes; Knowledge; Linkage Disequilibrium; Mental disorders; Meta-Analysis; Minority Groups; National Institute of Mental Health; Participant; Patients; Phase; Philanthropic Fund; Population; Population Heterogeneity; Psychiatry; Psychoses; Resolution; Risk; SNP genotyping; Sampling; Schizoaffective Disorders; Schizophrenia; Signal Transduction; Strategic Planning; Training; Variant; base; care outcomes; case control; cohort; genetic association; genome wide association study; genome-wide; genome-wide analysis; health disparity; improved; neuropsychiatry; non-genomic; novel; polygenic risk score; psychiatric genomics; screening; statistics; study population; whole genome

Project Summary We propose a 5-year renewal of our African Ancestry-Genomic Psychiatry Cohort (AA-GPC) R01- MH104964. AA and other minority populations have been poorly represented in large-scale genomic studies, and yet these populations (i) have the largest disparities in health care and outcomes, and (ii) have the potential to broaden our knowledge of human genetics. In particular, AA genomes have nearly a million more variants per individual and are characterized by shorter haplotype blocks than European ancestry (EA) populations. As a consequence, genetic polymorphisms that are in perfect linkage disequilibrium (LD) in Europeans are broken-up by recombination events in AA genomes, allowing the contributions of smaller genomic intervals comprised of fewer variants to be assessed independently. Progress to date: During the initial funding period we will have enrolled and assessed ~10,000 new AA participants and have already completed 8,000 AA whole genome sequences (WGS). We recently demonstrated that among the 128 associated SNPs identified in the PGC-2 schizophrenia analysis, 41 increased in significance when combined with data from 10,000 AA-GPC participants, and for 12 of these regions, there was a reduction in the number of SNPs in the associated interval. In addition, this trans-ancestry meta-analysis of PGC-2 schizophrenia and AA-GPC results yielded 10 newly genome-wide significant loci. Similarly, the trans-ancestry meta-analysis results yielded the best polygenic risk score “training” dataset, explaining more variance in individuals of European and African ancestry, than scores based on either ancestry alone. In Phase 1 of this renewal: we will study genome-wide common variation in our existing AA-GPC and VA-CS#572 combined cohort of 36,322 AA participants. In Phase 2, we will perform an expanded analysis by adding 5,000 new participants ascertained in this project, 27,500 additional controls from the VA, and 34,000 cases and controls from the NeuroGap-Psychosis study (NeuroPsychiatric Genetics in African Populations; PI. Koenen). This meta-analysis will include over 100,000 AA participants, a sample of non-Caucasians with the potential for significant novel discovery.

项目摘要 我们建议对我们的非洲遗传学-基因组精神病学队列（AA-GPC）R 01进行为期5年的更新， MH104964。AA和其他少数群体在大规模基因组研究中的代表性很差， 然而，这些人群（i）在医疗保健和结果方面的差距最大，（ii） 有可能扩大我们对人类遗传学的了解。特别是AA基因组有将近一百万个 每个个体都有变异，其特征是比欧洲血统（EA）更短的单倍型块 人口。因此，处于完美连锁不平衡（LD）的遗传多态性在 欧洲人被AA基因组中的重组事件打破，允许较小的贡献。 基因组区间由较少的变异组成，以独立评估。 迄今为止的进展：在最初的资助期间，我们将招募和评估约10，000名新的AA 参与者已经完成了8,000个AA全基因组序列（WGS）。我们最近 研究表明，在PGC-2精神分裂症分析中鉴定的128个相关SNP中， 当与来自10，000名AA-GPC参与者的数据相结合时，显着性增加，其中12人 区域中，在相关间隔中SNP的数量减少。此外，这种跨血统 PGC-2精神分裂症和AA-GPC结果的荟萃分析产生了10个新的全基因组显著位点。 类似地，跨祖先荟萃分析结果产生了最好的多基因风险评分“训练”数据集， 解释欧洲和非洲血统个体的差异，而不是基于 只有祖先。 在更新的第一阶段：我们将研究现有AA-GPC中的全基因组常见变异， VA-CS#572合并队列36，322例AA受试者。在第二阶段，我们将进行扩展分析， 增加了该项目中确定的5，000名新参与者、VA的27，500名额外控制人员和34，000名 来自NeuroGap-Psychosis研究的病例和对照（NeuroPsychiatric Genetics in African Populations; Pi. Koenen）。这项荟萃分析将包括超过100，000名AA参与者，一个非白人样本， 潜在的重大新发现。