Cross-Population Working Group on Genes and Environment in Major Depression (POP-GEM): Advancing the Understating of Etiology through Diversity

重度抑郁症基因与环境跨人群工作组 (POP-GEM)：通过多样性促进对病因的理解

• 批准号: 10375923
• 负责人: Roseann Elizabeth Peterson
• 金额: $ 84.77万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2022-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10375923
• 关键词: Address; African; Anxiety Disorders; Architecture; Asian; Catalogs; Collaborations; Data Collection; Data Set; Diagnosis; Disease; Ensure; Environment; Environmental Risk Factor; Etiology; European; Genes; Genetic; Genetic Population Study; Genetic Research; Genetic Risk; Genetic study; Genomics; Genotype; Goals; Heart Diseases; Human; Knowledge; Latino; Lead; Major Depressive Disorder; Medical; Mendelian randomization; Mental Depression; Mental disorders; Meta-Analysis; Methods; Modeling; National Institute of Mental Health; Obesity; Persons; Phase; Phenotype; Population; Population Analysis; Population Heterogeneity; Population Study; Prevalence; Prevention; Process; Research; Research Personnel; Resolution; Resources; Risk; Risk Factors; Role; Sampling; Sex Differences; Strategic Planning; Syndrome; Testing; Underrepresented Populations; Woman; Work; biobank; causal model; causal variant; clinical phenotype; clinically relevant; cohort; comorbid depression; comorbidity; data harmonization; disability; genetic approach; genetic architecture; genetic variant; genome wide association study; genome-wide; genomic variation; improved; insight; men; non-genomic; polygenic risk score; precision medicine; psychogenetics; study population; substance use; trait; working group

ABSTRACT Large-scale genetic studies of major depression (MD) are primarily comprised of European descent cohorts. Broadening diversity of study populations will empower genomic research by expanding discovery and enhancing our understanding of the role of human genomic variation in disease etiology. This proposal supports the formation of the Cross-Population Working Group on Genes and Environment in Major Depression (POP-GEM) with the goal of characterizing genomic variants associated with MD across ancestries. The overarching goal of this proposal is to leverage large-scale global collaborations to assemble extant and emerging datasets from diverse ancestries in order to perform the largest and most inclusive cross- population GWAS of MD to date (>70,000 diverse ancestry cases Phase I and >200,000 diverse ancestry cases Phase II). We will delineate the genetic architecture of MD across populations, facilitating fine-mapping of causal variants, improved polygenic risk profiling for all, examination of sex differences, and assessing direction of causation between major comorbid traits and disorders. This application presents an exceptional opportunity to gain insight into the etiology of MD and comorbid disease in groups underrepresented in prior genetics research. Our broad goal is to address the major limitations in our knowledge of the genetic and environmental risk architecture of MD in persons of diverse ancestries and lead to improvement in etiologic understanding, diagnosis, prevention, and treatment in all populations.

抽象的 重大抑郁症（MD）的大规模遗传研究主要由欧洲血统队列组成。 扩大研究人群的多样性将通过扩大发现和 增强我们对人类基因组变异在疾病病因学中的作用的理解。这个建议 支持主要在主要基因和环境的跨种群工作组的形成 抑郁症（流行游戏）的目的是表征与MD相关的基因组变体 祖先。该提案的总体目标是利用大规模的全球合作组装 来自不同祖先的现存和新兴数据集，以执行最大，最包容的跨界 迄今为止，医学博士的人口GWA（> 70,000种不同的血统案例，第一阶段和> 200,000种不同的血统 案例II阶段）。我们将在人群中描述MD的遗传结构，从而促进细映射 因果变体，所有人的多基因风险分析的改善，性别差异的检查和评估 主要合并性状和疾病之间因果关系的方向。此应用程序提出了一个杰出的 有机会深入了解MD和合并症的病因，以前的人数不足 遗传学研究。我们的广泛目标是解决我们对遗传和 MD在各种祖先的人中的环境风险架构，并改善病因 所有人群中的理解，诊断，预防和治疗。