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Cross-Population Working Group on Genes and Environment in Major Depression (POP-GEM)

Major depression (MD) is a leading cause of disability worldwide, arises from the action and interaction between genetic and environmental factors, and is often comorbid with other psychiatric and medical conditions. Although recent progress has yielded modest insight into the genetic architecture of MD, most studies have been in European ancestry populations, seriously limiting our knowledge of human genomic variation, disease etiology, and precision medicine efforts. Here, we propose cross-population genetic studies of MD to advance our understanding of the genetic architecture in all populations and ensure that genetic research is broadly applicable.

PsycheMERGE Diversity Initiative

A disproportionate majority of participants in large-scale genetic studies of severe mental illness (SMI) are of European descent, seriously limiting our knowledge of human genomic variation, disease etiology, and precision medicine efforts. The availability of large-scale biobanks linking electronic health records (EHRs) to biospecimens has created a powerful opportunity to rapidly expand ancestral representation in psychiatric research. Here, we form the PsycheMERGE Diversity Initiative to: (1) develop and validate EHR-based psychiatric phenotypes within underrepresented populations across multiple SMIs, (2) conduct within and cross-population genome-wide association studies, (3) improve and refine polygenic risk score profiling utilizing novel methods, and (4) improve fine-mapping of associated SMI variants through cross-ancestry fine-mapping approaches.

Cross-Ancestry GWAS for Major Depression in College Students

In the United States, major depressive disorder (MD) is a common psychiatric disorder. However, research into both psychiatric disorders and genome-wide association studies (GWAS) has historically focused on participants of European ancestry. The lack of diverse sampling reduces the generalizability of findings across populations. MD is a disorder that has risk factors that are both genetic and environmental in nature. To better understand risk factors for MD across diverse populations, we propose to examine cross-ancestry phenotypic and genetic associations in the Spit for Science (S4S) data including performing GWAS, estimating heritability, and genetic correlation across groups, and testing for sex differences.

CONVERGE Postpartum Depression

Postpartum depression (PPD) is the most common complication of childbirth and is associated with negative outcomes for both mother and child. Although a significant proportion of risk for both major depression (MD) and PPD is due to genetic factors, the degree of etiological distinction between PPD and MD is currently unknown. Increased genetic risk for PPD could actually reflect an underlying vulnerability to psychiatric illness, rather than PPD-specific genetic factors. To determine whether genetic risk for PPD is reflecting more psychiatric- or reproductive-related processes, we aim to explore the genetic interrelationship between PPD and several psychiatric and non-psychiatric reproductive-related traits. These questions will primarily be investigated in populations of East Asian ancestry, a group historically underrepresented in psychiatric genomics research.

GEDI: Genes, Puberty, & Depression

Associations between depression and reproductive-related traits, including age at puberty onset, have been observed, with some research supporting a causal effect between early maturation and depression risk. Although current evidence suggests that these correlations are likely driven by both biological (e.g., hormonal changes) and psychosocial environmental factors (e.g., lack of peer social support), the specific underlying biological processes linking these phenotypes have yet to be disentangled. Genome-wide association studies have identified significant genotypic correlations between age at menarche and depression, suggesting that shared genetic influences may partially explain the observed phenotypic correlations. 

However, it remains unclear whether these shared genetic influences are sustained throughout the life course. This study aims to provide additional insight into the biological processes underlying depression by investigating the genetic interrelationship between depression and age at pubertal onset in a subset of the Genes-Environment-Development Initiative (GEDI), a sample that combines genetic data with longitudinal measures from four cohorts.

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