Genomic signatures of inflammation: Pathways of racial discrimination, depressive symptoms, Vitamin D status with preterm birth among Black women

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Non-Hispanic Black women are 1.5 times more likely to have preterm birth (PTB; < 37 weeks gestation) compared with non-Hispanic White women (14% vs 9%). Preterm birth is the leading cause of neonatal morbidity among Black infants. Pregnant Black women are also more likely to experience racial discrimination and depressive symptoms and have higher risk for vitamin D deficiency [plasma 25(OH)D concentration <20 ng/ml] compared with White women. Racial discrimination, depressive symptoms and vitamin D deficiency have been associated with increased pro-inflammatory cytokines (e.g.,TNF-α, IL-6), but research has not examined the gene expression of immune-related genes as potential pathways of these factors with PTB. Peripheral mononuclear cells (PBMCs) contain lymphocytes, monocytes and dendritic cells all of which are important for immune function and can express both pro- and anti-inflammatory cytokines. By examining the gene expression pattern of PBMCs in a cohort of Black pregnant women, it could elucidate distinct or overlapping pathways by which psychosocial factors (e.g. racial discrimination, depressive symptoms) and vitamin D status increase risk for PTB. Using data from 168 pregnant Black women participating in Dr. Giurgescu's (mentor) R01 study, I will examine the associations among racial discrimination, depressive symptoms, Vitamin D Binding Protein (VDBP) genotype, plasma 25(OH)D concentration, gene expression of immune cell genes, systemic inflammation, and gestational age (GA) at birth. Women completed questionnaires and had blood drawn at 8- 18 weeks gestation. Questionnaire data, plasma cytokine (TNF-α, IL-6, IL-8, IL-4, IL-10, INF-γ) levels, and GA at birth will be available from the parent study. Frozen plasma and PBMC samples are stored in mentor's laboratory. Plasma 25(OH)D concentration will be measured from frozen samples using liquid chromatography/ mass spectrometry. VDBP genotype will be assessed by TaqMan assays using DNA extracted from nuclei isolated from PBMCs. Under the supervision of Dr. Kraus (co-mentor), I will conduct bulk RNA sequencing (RNA-seq) on frozen PBMCs. I aim to: (Aim 1) Explore differential gene expression of immune cell genes between (1) women with PTB and women with term birth; and (2) women with vitamin D deficiency and women with vitamin D sufficiency; and (Aim 2) Examine the pathways by which racial discrimination, depressive symptoms, plasma 25(OH)D, VDBP genotype, differentially expressed genes (identified in Aim 1), and systemic inflammation relate to GA at birth. The proposed, rigorous training plan and highly experienced mentorship team will accelerate my path to independent investigator, allowing me time to learn cutting-edge research using genomics and transcriptomics, develop competency in analysis and bioinformatics of omics data, and gain team leadership skills. The results from this study will provide the preliminary data for a NIH R01 study to identify predictive biomarkers for PTB.