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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.

PGC Cross Population Special Interest Group(SIG) 

The PGC Cross Population Special Interest Group (SIG) was formed in May of 2018 and it has 100+ members. The goal of the group is to support genetic analyses in diverse groups and ancestral populations through method development, empirical investigations, and support of collaborative projects.  The need for this group was evident from the fact that -- as of 2018 -- greater than 80 percent of genomic analyses had been conducted in exclusively European ancestry populations. Moreover, many leading genetics analysis methods were not yet suitable for use in different populations.  Fortunately, acknowledgement of these problems in genetics research has become widespread, and we formed this group as a means of accelerating progress in this important research area.

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.

All of Us Research Program

The All of Us Research Program is a historic effort to collect and study data from one million or more people living in the United States. The goal of the program is better health for all of us. Our mission is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us. This mission is carried out through three connected focus areas that are supported and made possible by a team that maintains a culture built around the program’s core values. All of Us is guided by core values such as transparency, diversity, and keeping participant information secure.

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