PROJECT SUMMARY We propose MomGenes Fight PPD: Expanding to Increase Participation from Diverse Ancestries to systematically investigate the genomic risk factors for postpartum depression (PPD) and their interplay with major environmental contributors. PPD affects ~500,000 women annually in the US, with an increased prevalence among black, indigenous, people of color (BIPOC) mothers. The effects of PPD are not only present in the mothers, but also can be seen in offspring at a critical developmental period. Despite the public health issues PPD poses, it is under-studied and its precise etiology is unknown. There is pressing need to develop methods for early detection of PPD for all women to mitigate severe outcomes and identify features of the disorder which can lead to personalized therapies. The need for diversity is evident across biomedical research and healthcare. Within genomics, increasing representation of BIPOC individuals results in improved locus discovery, fine-mapping, and genetic score accuracy. However, as we diversify research participants, we must also capture environmental contributors to PPD that disproportionately affect BIPOC women: adverse life events (ALE), which increase risk for PPD, and discrimination. Combined with our proposed increase in phenotyping and genetic analyses, we can have a more complete understanding of risk factors contributing to PPD. In 2016, we began the MomGenes Fight PPD study (formerly called PPD ACT) to power genome-wide association studies (GWAS) for PPD. Using our existing ascertainment platform, MomGenes will: Aim 1) expand the study to recruit 8,000 new samples (4,000 PPD cases and 4,000 ancestry-matched controls) from across the United States, focusing on BIPOC women and recontact ~12k existing MomGenes participants to collect deeper phenotypes; Aim 2) conduct trans-ancestry GWAS meta-analyses for PPD and a pre-planned set of secondary analyses using newly ascertained samples and existing PPD samples (~51,000 cases, ~141,000 controls from first GWAS and eight new cohorts); Aim 3) examine the impact of ALE (natural disaster, sexual abuse, physical abuse) and discrimination (racial, gender, religion, sexual orientation, weight) on PPD risk. This proposal expands on our team’s success in PPD genomics research. Samples collected in our initial MomGenes study contributed to the first PPD GWAS meta-analyses. With the proposed work, we will continue to build on this success, identifying genetic and environmental factors that increase risk for PPD. Ultimately, this can lead to actionable findings that aid all women suffering from PPD.