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

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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.