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.