Stress and Racial Disparities in Preeclampsia - Clues from DNA Methylomic Profiling

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Project Summary/Abstract Despite being one of the wealthiest developed nations, maternal mortality is on the rise in the U.S., almost doubling in the last thirty years. Racial disparities in maternal mortality have also widened, with Black maternal mortality more than three times that for White individuals. Studies exploring the social determinants of health have consistently identified inadequate prenatal care, poverty, and stress as areas partially responsible for the disparate burden of adverse pregnancy outcomes (APOs) such as preeclampsia among Black individuals. However, the stark racial disparity for Black individuals remains, even after adjusting for such socioeconomic and psychosocial factors. In order to narrow this disparity in preeclampsia, additional research to fully understand the cause is crucial. While race is a social construct, the consequences of this construct can have biological impact. Epigenomics represents a field where the impact of environmental and behavioral factors on gene expression can be explored and nuanced mechanisms of pathophysiology can be identified. The proposed analysis will allow us to leverage existing resources to address a key evidence gap in the literature regarding the epigenetic relationship between stress, race, and preeclampsia. The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (nuMoM2b) enrolled a diverse cohort of 10,038 healthy nulliparous women at 8 US academic medical centers during 2010-2013, who were followed from early in conception through the delivery of their first child. Extensive clinical phenotyping data exist for the pregnancy characteristics and pregnancy outcomes of these study participants. The nuMoM2b Heart Health Study is comprised of 7,003 nuMoM2b participants who were recontacted at least once after their nuMoM2b birth, 4,508 of whom returned for an in-person cardiovascular risk factor assessment 2-7 years later. A third study wave of in-person visits will begin in early 2022. This cohort is thus uniquely positioned to address questions about the role of stress in the pathophysiology of preeclampsia. With this administrative supplement, we will capitalize on existing samples and data to (1) identify factors that contribute to greater risk for development of preeclampsia in Black individuals compared to White individuals, (2) produce a large methylation data set that will add another layer to existing data (GWAS, proteomics), resulting in the largest multi-omics data set of pregnant individuals in the U.S., that (3) can be leveraged for future longitudinal analyses that examine how stress, self-identified race, other behavioral factors, and preeclampsia contribute to the emergence of cardiovascular disease in years following pregnancy.