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

摘要 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。这项建议 支持成立跨人群基因与环境工作组， 抑郁症（POP-GEM），目的是表征与MD相关的基因组变异， 祖先该提案的总体目标是利用大规模的全球合作， 现有的和新兴的数据集来自不同的祖先，以执行最大和最具包容性的交叉， 迄今为止MD的人群GWAS（> 70，000例不同血统病例I期和> 200，000例不同血统病例 第二阶段）。我们将描绘不同人群中MD的遗传结构，促进精细定位 的因果变异，改进多基因风险分析，检查性别差异，并评估 主要共病特征和疾病之间的因果关系方向。该应用程序提供了一个特殊的 有机会在既往研究中代表性不足的人群中深入了解MD和共病的病因 遗传学研究我们的广泛目标是解决我们对遗传学知识的主要局限性， 不同血统人群中MD的环境风险结构，并导致病因学的改善 了解、诊断、预防和治疗。

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.